Background: Hip osteoarthritis (HOA) causes joint destruction, resulting in hip pain, limited range-of-motion, claudication, and joint deformity. In the conservative treatment of HOA, self-management is important to m...Background: Hip osteoarthritis (HOA) causes joint destruction, resulting in hip pain, limited range-of-motion, claudication, and joint deformity. In the conservative treatment of HOA, self-management is important to manage symptoms and control disease progression. In a previous study, the researchers conducted a conceptual analysis of 43 foreign studies on self-management during conservative therapy for patients with HOA. The results revealed a definition of self-management during conservative therapy for patients with HOA. However, because that study analyzed only the foreign literature, it remains unclear whether the findings reflect the characteristics of the Japanese health-care delivery system, health-care insurance system, or the lifestyles and cultural characteristics of Japanese patients with HOA. Objective: We aimed to clarify the self-management behaviors of patients with HOA. Methods: Semi-structured interviews were conducted with five patients diagnosed with HOA, and the results were subjected to inductive qualitative analysis. Results: Six categories of self-management behaviors were extracted for patients with HOA: [active information gathering about HOA], [personalized pain and weight management, and strategies for reducing hip joint load], [reflection on living conditions with individuals and professionals, and determination for future efforts], [continuation of exercise and weight management based on personal strengths and achievements, and mutual support with others], [coexistence with HOA while managing negative feelings], and [choosing treatment methods by trusting doctors while struggling with personal needs]. Conclusion: These findings suggest the need to develop health guidance and educational programs for patients with HOA that focus on how to prevent disease progression and cope with symptoms.展开更多
Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,ha...Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.展开更多
The ambiguity of etiology makes temporomandibular joint osteoarthritis(TMJOA)“difficult-to-treat”.Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management.Nonetheless,challenges...The ambiguity of etiology makes temporomandibular joint osteoarthritis(TMJOA)“difficult-to-treat”.Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management.Nonetheless,challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances.Addressing lower strontium(Sr)levels in arthritic synovial microenvironment,we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells(SMSCs).Here,we developed an optimized system that boosts the yield of SMSC-derived exosomes(SMSCEXOs)and improves their miRNA profiles with an elevated proportion of beneficial miRNAs,while reducing harmful ones by pretreating SMSCs with Sr.Compared to untreated SMSC-EXOs,Sr-pretreated SMSC-derived exosomes(Sr-SMSC-EXOs)demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA.Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading,identifying miR-143-3p as a key anti-TMJOA exosomal component.Interestingly,this system is specifically oriented towards synovium-derived stem cells.The insight into trace elementdriven,site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.展开更多
BACKGROUND Osteoarthritis(OA)is a prevalent joint disorder requiring innovative treatment approaches.AIM To evaluate the use of nanofat,a specialized form of adipose tissue-derived cells,in the treatment of OA,by exam...BACKGROUND Osteoarthritis(OA)is a prevalent joint disorder requiring innovative treatment approaches.AIM To evaluate the use of nanofat,a specialized form of adipose tissue-derived cells,in the treatment of OA,by examining its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term outcomes.METHODS A comprehensive review of preclinical studies,clinical trials,and in vitro investigations was conducted.The included studies provided insights into the potential role of nanofat in OA treatment,addressing its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term outcomes.RESULTS Clinical studies consistently reported the efficacy of nanofat in providing pain relief and functional improvement in patients with OA.Local adverse events were limited to the injection site,such as localized pain and inflammation,and resolved within a few days to weeks.Systemic adverse events were rare,and no significant long-term complications were observed.Mechanistically,nanofat was found to enhance chondrocyte proliferation,reduce inflammation,and promote angiogenesis,thereby contributing to its therapeutic effects.CONCLUSION Nanofat therapy holds promise as a therapeutic option for managing OA,providing pain relief,functional improvement,and potential tissue regeneration.The safety profile of nanofat treatment appears favorable,but long-term data are still limited.Standardized protocols,larger randomized controlled trials,longer follow-up periods,and cost-effectiveness evaluations are warranted to establish optimal protocols,comparative effectiveness,and long-term outcomes.Despite current limitations,nanofat therapy demonstrates translational potential and should be considered in clinical practice for OA treatment,with careful patient selection and monitoring.展开更多
This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The result...This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The results showed that NhUCMSCs alleviated osteoarthritis-related cartilage damage and inflammation comparably to both serum-cultured hUCMSCs and hyaluronic acid.While these findings broaden the potential clinical utility of N-hUCMSCs by circumventing certain drawbacks of serum-based cultures,the equivalence in efficacy raises important questions.First,how do N-hUCMSCs differ phenotypically from serum-cultured hUCMSCs,particularly in terms of proliferation rate,replicative capacity,and senescence profile?Second,what advantages might N-hUCMSCs offer over hyaluronic acid-a well-established therapy-beyond avoiding xenogeneic components and ethical concerns?Future research should focus on longterm phenotypic stability,sustained functional benefits,safety profiles,and mechanistic insights to ascertain whether N-hUCMSCs can surpass current standards of care.展开更多
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem...Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.展开更多
Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poo...Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.展开更多
BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more rese...BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.展开更多
BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflamm...BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.展开更多
Background:Osteoarthritis(OA)is a common joint disease,and existing drugs cannot cure OA,so there is an urgent need to identify new targets.Mitophagy plays an important role in OA;however,the role of mitophagy in the ...Background:Osteoarthritis(OA)is a common joint disease,and existing drugs cannot cure OA,so there is an urgent need to identify new targets.Mitophagy plays an important role in OA;however,the role of mitophagy in the OA immune system is not yet clear.Methods:In this study,differential analysis and enrichment analysis were used to identify mitophagy-related genes(MRGs)with differential expression in OA and the functional pathways involved in OA.Subsequently,two machine learning methods,RF and LASSO,were used to screen MRGs with diagnostic value and construct nomograms.At the same time,the relationship between mitophagy and OA immune response was explored by immunoinfiltration analysis.Results:Forty-three differentially MRGs were identified in OA,of which six MRGs(GABARAPL2,PARL,GABARAPL1,JUN,RRAS,and SNX7)were associated with the diagnosis of OA.The ROC analysis results show that these 6 MRGs have high predictive accuracy in the diagnosis of OA.In immune infiltration analysis,we found that the abundance of significantly different immune cells in OA was mostly upregulated.In addition,the expression of diagnostic-related MRGs is correlated with changes in the abundance of immune cells in OA.Conclusion:This study demonstrates that six MRGs can be used as diagnostic biomarkers.The expression of diagnostic-related MRGs is correlated with changes in the abundance of immune cells in OA.At the same time,mitophagy may affect the immune microenvironment of OA by regulating immune cells,ultimately leading to the progression of OA.展开更多
BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to pat...BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.展开更多
Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage...Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.展开更多
Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leadi...Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.展开更多
Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical features.It is a major public health problem worldwide and it imposes serious medical and eco...Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical features.It is a major public health problem worldwide and it imposes serious medical and economic burdens.KOA accounts for nearly four-fifths of the global Osteoarthritis burden and increases with rising obesity and age[1].There are many reasons for the change in disease prevalence and risk factors,such as urbanization,lifestyle changes,population aging,and sex imbalances.展开更多
Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes an...Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.展开更多
Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to id...Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.展开更多
Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. Methodology: This was an analyti...Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. Methodology: This was an analytical cross-sectional study carried out in the rheumatology department of the Cocody UTH in Abidjan (Ivory Coast) from March 1 to April 30 2023. Patients who came for rheumatology consultation presenting with mechanical arthralgia of the lower limbs, who were obese, had radiographic images were included. All patients without radiographic images were excluded. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m. The Chi<sup>2</sup> test was used to compare proportions and determine the existence of associations between osteoarthristis and obesity, obesity severity and radiographic stage of osteoarthritis as well as the functional impact. A p-value below a predefined threshold (p = 0,05) indicates a significant relationship between the variables. Result: Out of 185 patients received for osteoarthritis of the lower limbs during the study period, 136 were obese (74%). There were 115 women (84.6%) with an average age of 56.03 with a standard deviation of 12.72 years (extremes: 22 and 84 years). The main socio-professional category was the informal sector (30%). The majority of patients had a low socio-economic level (80.2%) and lived in urban areas (92.6%). The most common past medical history was hypertension (33.08%) followed by peptic ulcer disease (16.91%). Patients had a body mass index class 1 (81.6%), class 2 (15.40%) and class 3 (2.90%). The average duration of symptom progression until diagnosis was 11 months. Genu varum was the main static disorder (56.10%) and the knee joint was the dominant topography (90.4%) with a bilateral localization (80%). The average Lequesne index was greater than 8 (59.5%). The Kellgren and Lawrence radiographic stages were stage 1 (9.20%), stage 2 (46.90%), stage 3 (29.20%) and stage 4 (6.90%). The Obesity severity was significantly associated with osteoarthritis of the knee (p = 0.042). There was no statistically significant association between obesity severity and radiographic stage of osteoarthritis (p = 0.163) or functional impact (p = 0.180). Conclusion: Osteoarthritis of the lower limbs affected obese women and was dominated by stage 2 osteoarthritis of the knee (Kellgren and Lawrence). There is an association between the severity of obesity and osteoarthritis of the knee.展开更多
Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acup...Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.展开更多
文摘Background: Hip osteoarthritis (HOA) causes joint destruction, resulting in hip pain, limited range-of-motion, claudication, and joint deformity. In the conservative treatment of HOA, self-management is important to manage symptoms and control disease progression. In a previous study, the researchers conducted a conceptual analysis of 43 foreign studies on self-management during conservative therapy for patients with HOA. The results revealed a definition of self-management during conservative therapy for patients with HOA. However, because that study analyzed only the foreign literature, it remains unclear whether the findings reflect the characteristics of the Japanese health-care delivery system, health-care insurance system, or the lifestyles and cultural characteristics of Japanese patients with HOA. Objective: We aimed to clarify the self-management behaviors of patients with HOA. Methods: Semi-structured interviews were conducted with five patients diagnosed with HOA, and the results were subjected to inductive qualitative analysis. Results: Six categories of self-management behaviors were extracted for patients with HOA: [active information gathering about HOA], [personalized pain and weight management, and strategies for reducing hip joint load], [reflection on living conditions with individuals and professionals, and determination for future efforts], [continuation of exercise and weight management based on personal strengths and achievements, and mutual support with others], [coexistence with HOA while managing negative feelings], and [choosing treatment methods by trusting doctors while struggling with personal needs]. Conclusion: These findings suggest the need to develop health guidance and educational programs for patients with HOA that focus on how to prevent disease progression and cope with symptoms.
文摘Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.
基金supported by National Natural Science Foundation of China(Nos.82271019,82472149,82471024)Sichuan Science and Technology Program(No.24ZDYF0099)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202101)to J.W.
文摘The ambiguity of etiology makes temporomandibular joint osteoarthritis(TMJOA)“difficult-to-treat”.Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management.Nonetheless,challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances.Addressing lower strontium(Sr)levels in arthritic synovial microenvironment,we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells(SMSCs).Here,we developed an optimized system that boosts the yield of SMSC-derived exosomes(SMSCEXOs)and improves their miRNA profiles with an elevated proportion of beneficial miRNAs,while reducing harmful ones by pretreating SMSCs with Sr.Compared to untreated SMSC-EXOs,Sr-pretreated SMSC-derived exosomes(Sr-SMSC-EXOs)demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA.Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading,identifying miR-143-3p as a key anti-TMJOA exosomal component.Interestingly,this system is specifically oriented towards synovium-derived stem cells.The insight into trace elementdriven,site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
文摘BACKGROUND Osteoarthritis(OA)is a prevalent joint disorder requiring innovative treatment approaches.AIM To evaluate the use of nanofat,a specialized form of adipose tissue-derived cells,in the treatment of OA,by examining its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term outcomes.METHODS A comprehensive review of preclinical studies,clinical trials,and in vitro investigations was conducted.The included studies provided insights into the potential role of nanofat in OA treatment,addressing its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term outcomes.RESULTS Clinical studies consistently reported the efficacy of nanofat in providing pain relief and functional improvement in patients with OA.Local adverse events were limited to the injection site,such as localized pain and inflammation,and resolved within a few days to weeks.Systemic adverse events were rare,and no significant long-term complications were observed.Mechanistically,nanofat was found to enhance chondrocyte proliferation,reduce inflammation,and promote angiogenesis,thereby contributing to its therapeutic effects.CONCLUSION Nanofat therapy holds promise as a therapeutic option for managing OA,providing pain relief,functional improvement,and potential tissue regeneration.The safety profile of nanofat treatment appears favorable,but long-term data are still limited.Standardized protocols,larger randomized controlled trials,longer follow-up periods,and cost-effectiveness evaluations are warranted to establish optimal protocols,comparative effectiveness,and long-term outcomes.Despite current limitations,nanofat therapy demonstrates translational potential and should be considered in clinical practice for OA treatment,with careful patient selection and monitoring.
基金Supported by the Natural Science Foundation of Shanghai,No.24ZR1459300(to Xiao-Ting Liang)and the Pyramid Talent Project,No.YQ677(to Yue Ding).
文摘This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The results showed that NhUCMSCs alleviated osteoarthritis-related cartilage damage and inflammation comparably to both serum-cultured hUCMSCs and hyaluronic acid.While these findings broaden the potential clinical utility of N-hUCMSCs by circumventing certain drawbacks of serum-based cultures,the equivalence in efficacy raises important questions.First,how do N-hUCMSCs differ phenotypically from serum-cultured hUCMSCs,particularly in terms of proliferation rate,replicative capacity,and senescence profile?Second,what advantages might N-hUCMSCs offer over hyaluronic acid-a well-established therapy-beyond avoiding xenogeneic components and ethical concerns?Future research should focus on longterm phenotypic stability,sustained functional benefits,safety profiles,and mechanistic insights to ascertain whether N-hUCMSCs can surpass current standards of care.
基金This work was supported by grants from National Natural Science Foundation of China(81830078,82071868,32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+2 种基金Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Shanghai Key Laboratory of Orthopedic Implant(No.KFKT202206).
文摘Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
基金supported by the Cutting Edge Development Fund of Advanced Medical Research Institute(GYY2023QY01)the China Postdoctoral Science Foundation(certificate number:2023M732093)。
文摘Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.
文摘BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.
基金Project of the National Natural Science Foundation of China,No.82172398Key Research Project of the Department of Education of Liaoning Province,No.LJKZZ20220148+1 种基金Dalian Medical Science Research Project,No.2111038Dalian Dengfeng Plan Medical Key Specialty Construction Project(2021),No.243.
文摘BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.
基金supported by Zunyi Science and Technology Bureau and the First People's Hospital of Zunyi joint science and Technology Research and development fund project (No.Zun City Science and HZ word (2023)16)Guizhou Province Science and Technology Program Project (No.Guizhou Science and Technology-ZK[2021]General 393)+1 种基金Guizhou Province Science and Technology Program Project (No.Guizhou Synthetic Fruit-LC[2022]029)Guizhou Provincial Health Commission Science and Technology (No.gzwkj2021-259)。
文摘Background:Osteoarthritis(OA)is a common joint disease,and existing drugs cannot cure OA,so there is an urgent need to identify new targets.Mitophagy plays an important role in OA;however,the role of mitophagy in the OA immune system is not yet clear.Methods:In this study,differential analysis and enrichment analysis were used to identify mitophagy-related genes(MRGs)with differential expression in OA and the functional pathways involved in OA.Subsequently,two machine learning methods,RF and LASSO,were used to screen MRGs with diagnostic value and construct nomograms.At the same time,the relationship between mitophagy and OA immune response was explored by immunoinfiltration analysis.Results:Forty-three differentially MRGs were identified in OA,of which six MRGs(GABARAPL2,PARL,GABARAPL1,JUN,RRAS,and SNX7)were associated with the diagnosis of OA.The ROC analysis results show that these 6 MRGs have high predictive accuracy in the diagnosis of OA.In immune infiltration analysis,we found that the abundance of significantly different immune cells in OA was mostly upregulated.In addition,the expression of diagnostic-related MRGs is correlated with changes in the abundance of immune cells in OA.Conclusion:This study demonstrates that six MRGs can be used as diagnostic biomarkers.The expression of diagnostic-related MRGs is correlated with changes in the abundance of immune cells in OA.At the same time,mitophagy may affect the immune microenvironment of OA by regulating immune cells,ultimately leading to the progression of OA.
文摘BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.
文摘Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.
文摘Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.
基金funded by the Capital Health Research and Development of Special Funds(NO:2022-1-7032)the High-level Talent Research Project of Beijing University of Chinese Medicine(NO2021-XJ-KYQD-001).
文摘Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical features.It is a major public health problem worldwide and it imposes serious medical and economic burdens.KOA accounts for nearly four-fifths of the global Osteoarthritis burden and increases with rising obesity and age[1].There are many reasons for the change in disease prevalence and risk factors,such as urbanization,lifestyle changes,population aging,and sex imbalances.
基金supported by the National Key R&D Program of China(2022YFB4600600)National Natural Science Foundation of China(32271181,82301785)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2020B1515120001)Sichuan Province Central Guided Local Science and Technology Development Special Program(2023ZYD0072).
文摘Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.
文摘Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.
文摘Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. Methodology: This was an analytical cross-sectional study carried out in the rheumatology department of the Cocody UTH in Abidjan (Ivory Coast) from March 1 to April 30 2023. Patients who came for rheumatology consultation presenting with mechanical arthralgia of the lower limbs, who were obese, had radiographic images were included. All patients without radiographic images were excluded. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m. The Chi<sup>2</sup> test was used to compare proportions and determine the existence of associations between osteoarthristis and obesity, obesity severity and radiographic stage of osteoarthritis as well as the functional impact. A p-value below a predefined threshold (p = 0,05) indicates a significant relationship between the variables. Result: Out of 185 patients received for osteoarthritis of the lower limbs during the study period, 136 were obese (74%). There were 115 women (84.6%) with an average age of 56.03 with a standard deviation of 12.72 years (extremes: 22 and 84 years). The main socio-professional category was the informal sector (30%). The majority of patients had a low socio-economic level (80.2%) and lived in urban areas (92.6%). The most common past medical history was hypertension (33.08%) followed by peptic ulcer disease (16.91%). Patients had a body mass index class 1 (81.6%), class 2 (15.40%) and class 3 (2.90%). The average duration of symptom progression until diagnosis was 11 months. Genu varum was the main static disorder (56.10%) and the knee joint was the dominant topography (90.4%) with a bilateral localization (80%). The average Lequesne index was greater than 8 (59.5%). The Kellgren and Lawrence radiographic stages were stage 1 (9.20%), stage 2 (46.90%), stage 3 (29.20%) and stage 4 (6.90%). The Obesity severity was significantly associated with osteoarthritis of the knee (p = 0.042). There was no statistically significant association between obesity severity and radiographic stage of osteoarthritis (p = 0.163) or functional impact (p = 0.180). Conclusion: Osteoarthritis of the lower limbs affected obese women and was dominated by stage 2 osteoarthritis of the knee (Kellgren and Lawrence). There is an association between the severity of obesity and osteoarthritis of the knee.
基金supported by the National Natural Science Foundation of China(82074523)the National Natural Youth Science Foundation of China(82004448).
文摘Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.
