Shoulder stiffness(SS)is a common shoulder disease characterized by increasing pain and limited range of motion.SS is considered to be an inflammatory and fibrotic disorder pathologically.However,there is no consensus...Shoulder stiffness(SS)is a common shoulder disease characterized by increasing pain and limited range of motion.SS is considered to be an inflammatory and fibrotic disorder pathologically.However,there is no consensus on the most effective conservative treatment for fibrosis.Given that human Bone Marrow Mesen-chymal Stem Cell-derived extracellular vesicles(BMSC-EVs)displayed promising therapeutic effects for various tissues,we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models.By conducting a series of experiments,we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo.In detail,BMSC-EVs suppressed the aberrant proliferation,high collagen production capacity,and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro.Besides,in vivo,BMSC-EVs reduced cell infiltration,reduced fibrotic tissue in the shoulder capsule,and improved shoulder mobility.In addition,via exosomal small RNA sequencing and qPCR analysis,let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs.The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p.Moreover,we discovered that the mRNA of TGFBR1(the membrane receptor of transforming growth factorβ)was the target of let-7a-5p.Together,these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis.This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy,which may clinically benefit patients with SS in the future.展开更多
A frozen shoulder is a common cause of shoulder pain and stiffness.The etiology and pathology of frozen shoulders is not fully understood yet.Frozen shoulderis characterized by a decrease in intra-articular volume and...A frozen shoulder is a common cause of shoulder pain and stiffness.The etiology and pathology of frozen shoulders is not fully understood yet.Frozen shoulderis characterized by a decrease in intra-articular volume and capsular compliance.This can lead to significant limitations in daily life.The majority of the patients can be treated conservatively,with functional recovery to be expected in two to three years.However,if conservative treatment fails,manipulation under anaesthesia and arthroscopic capsular release can both be considered as appropriate treatments.Manipulation is a traditionally well-established technique but in recent years it seems that arthroscopic capsular release has gained popularity.Manipulation is a relative time efficient and technically low-demanding procedure in which the glenohumeral joint is forced into different directions under general anaesthesia to release the capsular contracture,thereby increasing the range of motion of the joint.In arthroscopic capsular release the glenohumeral capsule can be released in a more controlled manner under direct vision.There are no prospective comparative trials available to display superiority of one procedure over the other.In addition,the optimal timing of both these interventions still has to be determined.An overview of the literature concerning this topic and a description of both procedures with its own advantages and disadvantages is provided.展开更多
As the background of our study, we requested that practitioners use muscle hardness testers to conduct a digital assessment of muscle hardness layers that they can feel by palpation. We developed muscle hardness teste...As the background of our study, we requested that practitioners use muscle hardness testers to conduct a digital assessment of muscle hardness layers that they can feel by palpation. We developed muscle hardness testers to assess muscle hardness digitally from the reaction force and the depth in pushing a finger-shaped indenter, thereby simulating palpation. To assess muscle hardness digitally, we proposed this means using the reaction force and depth that are measured when the indenter is pushed, along with the elastic constant, and the differential elastic modulus. The tester is designed to be useful to ascertain effects of, or follow the course of, muscle layer treatment applied for shoulder stiffness and other conditions. As described herein, we confirmed the effectiveness of digital assessment using foam rubber consisting of an upper layer and a lower layer, respectively simulating the cortical and muscle layers of a human body. Additionally, monitoring six subjects, we digitally assessed the change of hardness of the trapezius muscle by changing the position of the upper extremity. Next, we were able to measure the change of hardness before and after treatment for 21 subjects with shoulder stiffness.展开更多
文摘Shoulder stiffness(SS)is a common shoulder disease characterized by increasing pain and limited range of motion.SS is considered to be an inflammatory and fibrotic disorder pathologically.However,there is no consensus on the most effective conservative treatment for fibrosis.Given that human Bone Marrow Mesen-chymal Stem Cell-derived extracellular vesicles(BMSC-EVs)displayed promising therapeutic effects for various tissues,we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models.By conducting a series of experiments,we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo.In detail,BMSC-EVs suppressed the aberrant proliferation,high collagen production capacity,and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro.Besides,in vivo,BMSC-EVs reduced cell infiltration,reduced fibrotic tissue in the shoulder capsule,and improved shoulder mobility.In addition,via exosomal small RNA sequencing and qPCR analysis,let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs.The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p.Moreover,we discovered that the mRNA of TGFBR1(the membrane receptor of transforming growth factorβ)was the target of let-7a-5p.Together,these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis.This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy,which may clinically benefit patients with SS in the future.
文摘A frozen shoulder is a common cause of shoulder pain and stiffness.The etiology and pathology of frozen shoulders is not fully understood yet.Frozen shoulderis characterized by a decrease in intra-articular volume and capsular compliance.This can lead to significant limitations in daily life.The majority of the patients can be treated conservatively,with functional recovery to be expected in two to three years.However,if conservative treatment fails,manipulation under anaesthesia and arthroscopic capsular release can both be considered as appropriate treatments.Manipulation is a traditionally well-established technique but in recent years it seems that arthroscopic capsular release has gained popularity.Manipulation is a relative time efficient and technically low-demanding procedure in which the glenohumeral joint is forced into different directions under general anaesthesia to release the capsular contracture,thereby increasing the range of motion of the joint.In arthroscopic capsular release the glenohumeral capsule can be released in a more controlled manner under direct vision.There are no prospective comparative trials available to display superiority of one procedure over the other.In addition,the optimal timing of both these interventions still has to be determined.An overview of the literature concerning this topic and a description of both procedures with its own advantages and disadvantages is provided.
文摘As the background of our study, we requested that practitioners use muscle hardness testers to conduct a digital assessment of muscle hardness layers that they can feel by palpation. We developed muscle hardness testers to assess muscle hardness digitally from the reaction force and the depth in pushing a finger-shaped indenter, thereby simulating palpation. To assess muscle hardness digitally, we proposed this means using the reaction force and depth that are measured when the indenter is pushed, along with the elastic constant, and the differential elastic modulus. The tester is designed to be useful to ascertain effects of, or follow the course of, muscle layer treatment applied for shoulder stiffness and other conditions. As described herein, we confirmed the effectiveness of digital assessment using foam rubber consisting of an upper layer and a lower layer, respectively simulating the cortical and muscle layers of a human body. Additionally, monitoring six subjects, we digitally assessed the change of hardness of the trapezius muscle by changing the position of the upper extremity. Next, we were able to measure the change of hardness before and after treatment for 21 subjects with shoulder stiffness.
