In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast d...In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that展开更多
INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric ...INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.展开更多
RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem...RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells(BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs.Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rank: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.展开更多
骨形成是参与维持机体骨稳态的重要途径之一,其功能障碍可介导多类骨代谢疾患的发生发展。研究发现Wnt/β-连环蛋白(Wnt/β-catenin)、腺苷酸活化蛋白激酶/沉默信息调节因子1(adenylate-activated protein kinase/silent information re...骨形成是参与维持机体骨稳态的重要途径之一,其功能障碍可介导多类骨代谢疾患的发生发展。研究发现Wnt/β-连环蛋白(Wnt/β-catenin)、腺苷酸活化蛋白激酶/沉默信息调节因子1(adenylate-activated protein kinase/silent information regulator 1,AMPK/SIRT1)、细胞外调节蛋白激酶1/2-转录因子核心结合因子α1(extracellular regulated protein kinase 1/2-transcription factor core binding factorα1,ERK1/2-Cbfa1)、p38丝裂原蛋白活化激酶(p38 mitogen-activated kinase,p38 MAPK)、核转录因子-κB(nuclear transcription factor-κB,NF-κB)、Notch等多条信号通路均有干预骨形成、调控骨稳态的潜能。机械牵张作为调节细胞增殖、分化的重要手段,运用合理的牵张方式可对参与骨形成、维持骨稳态的多类细胞产生积极调控作用。本文通过对机械牵张干预上述信号通路影响骨形成的相关文献进行综述,旨在进一步明确机械牵张干预骨形成的作用机制,以期为经机械牵张正向调控骨代谢相关疾患的发展态势提供思路和理论依据。展开更多
骨形态发生ⅠA型受体(bone morphogenetic protein receptorⅠA,BMPRⅠA)在骨代谢疾病中发挥关键作用。BMP受体与转化生长因子β(TGF-β)配体结合传递信号,介导成骨细胞性骨形成与破骨细胞性骨吸收,参与骨发育、重塑等骨代谢过程。中药...骨形态发生ⅠA型受体(bone morphogenetic protein receptorⅠA,BMPRⅠA)在骨代谢疾病中发挥关键作用。BMP受体与转化生长因子β(TGF-β)配体结合传递信号,介导成骨细胞性骨形成与破骨细胞性骨吸收,参与骨发育、重塑等骨代谢过程。中药在防治骨代谢疾病方面历史悠久,对骨量、骨质量的促进作用显著。本文综述了BMPRⅠA与骨代谢疾病的作用机制,总结干预BMPRⅠA及其信号通路调节骨代谢的中药研究现状,以期为后续的药物研究提供思路。展开更多
目的概述STING信号通路在骨质疏松中的作用机制与研究成果,从而为骨质疏松的治疗提供新的思路。方法于2023年11月在PubMed和中国知网数据库中以“STING、osteoporosis、osteoblast、osteoclast、IFN-β、NF-κB、type H vessels”为英...目的概述STING信号通路在骨质疏松中的作用机制与研究成果,从而为骨质疏松的治疗提供新的思路。方法于2023年11月在PubMed和中国知网数据库中以“STING、osteoporosis、osteoblast、osteoclast、IFN-β、NF-κB、type H vessels”为英文检索词进行检索,以“STING信号通路、成骨细胞、破骨细胞、IFN-β、NF-κB、H型血管”为中文检索词进行检索。结果通过阅读标题及摘要进行文献筛选,最终引用论文数41篇。结论STING通路为骨质疏松症中的治疗提供了新的方向。激活STING/IFN-β信号通路可抑制破骨细胞分化,抑制骨吸收。而STING/NF-κB信号可导致骨吸收增加、骨形成减少。此外,STING信号通路的激活可抑制具有成骨能力的H型血管的产生,从而抑制骨形成。因此,STING通路在骨质疏松疾病进展中具有双重调控作用,调控STING通路的不同分支有望发展更为有效的骨质疏松症治疗方法。展开更多
文摘In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that
基金supported by grants by NIH grant AR-044741(Y-PL) and R01DE023813 (Y-PL)
文摘INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.
基金supported by the National Natural Science Foundation (NNSF) Key Research Program in Aging (91749204)National Natural Science Foundation of China (81871099, 31370958, 81701364, 81771491, 81501052)+1 种基金Shanghai Municipal Science and Technology Commission Key Program (15411950600, 18431902300)Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai (2017BR011)
文摘RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells(BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs.Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rank: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.
文摘骨形态发生ⅠA型受体(bone morphogenetic protein receptorⅠA,BMPRⅠA)在骨代谢疾病中发挥关键作用。BMP受体与转化生长因子β(TGF-β)配体结合传递信号,介导成骨细胞性骨形成与破骨细胞性骨吸收,参与骨发育、重塑等骨代谢过程。中药在防治骨代谢疾病方面历史悠久,对骨量、骨质量的促进作用显著。本文综述了BMPRⅠA与骨代谢疾病的作用机制,总结干预BMPRⅠA及其信号通路调节骨代谢的中药研究现状,以期为后续的药物研究提供思路。
文摘目的概述STING信号通路在骨质疏松中的作用机制与研究成果,从而为骨质疏松的治疗提供新的思路。方法于2023年11月在PubMed和中国知网数据库中以“STING、osteoporosis、osteoblast、osteoclast、IFN-β、NF-κB、type H vessels”为英文检索词进行检索,以“STING信号通路、成骨细胞、破骨细胞、IFN-β、NF-κB、H型血管”为中文检索词进行检索。结果通过阅读标题及摘要进行文献筛选,最终引用论文数41篇。结论STING通路为骨质疏松症中的治疗提供了新的方向。激活STING/IFN-β信号通路可抑制破骨细胞分化,抑制骨吸收。而STING/NF-κB信号可导致骨吸收增加、骨形成减少。此外,STING信号通路的激活可抑制具有成骨能力的H型血管的产生,从而抑制骨形成。因此,STING通路在骨质疏松疾病进展中具有双重调控作用,调控STING通路的不同分支有望发展更为有效的骨质疏松症治疗方法。
