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
背景:正畸力通过多种信号通路激活牙周组织自噬,进一步增强或减弱相关细胞(牙周膜细胞、骨细胞、破骨细胞和成骨细胞等)的活性来促进牙周重塑。目的:综述目前正畸力介导牙周组织自噬的研究进展和其对正畸牙齿移动的影响。方法:在PubMed...背景:正畸力通过多种信号通路激活牙周组织自噬,进一步增强或减弱相关细胞(牙周膜细胞、骨细胞、破骨细胞和成骨细胞等)的活性来促进牙周重塑。目的:综述目前正畸力介导牙周组织自噬的研究进展和其对正畸牙齿移动的影响。方法:在PubMed、Web of Science、中国生物医学文献数据库和中国知网数据库进行文献检索,设置检索时限为2010-2023年,总结了2010年以来正畸与自噬相关研究进展,最终纳入76篇文献进行分析讨论。结果与结论:(1)正畸力可通过牙周机械感受器和其造成的无菌性炎症引发一系列生物化学信号的转变,进而引起牙周组织自噬。(2)自噬通过级联放大的信号通路如磷脂酰肌醇-3-激酶/蛋白激酶B通路、河马通路及丝裂原活化蛋白激酶通路等,产生相应反馈从而促进牙周组织改建,最终实现牙齿的移动与稳定。正畸力诱导的自噬可差异性调节牙齿压力侧骨吸收和张力侧骨形成,相关靶点在正畸临床治疗的应用中具有良好前景。(3)然而,正畸力与自噬的机制较为复杂,现有研究仅停留在探究自噬对正畸牙齿移动的作用,自噬与正畸牙齿移动过程中的相互调节作用、涉及相关通路上游机械受体及信号通路间的交互作用均需要进一步的探究。展开更多
Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli tr...Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli transmitted by integrins influence the cytoskeleton, in turn, the cytoskeleton influences cell adhesion via integrins, then cell adhesion results in a series of signal transduction cascades. In skeleton, integrins also have a key role for bone resoption by osteoclasts and reformation by osteoblasts. In present review, the proteins involved in integrin signal transduction and integrin signal transduction pathways were discussed, mainly on the basic mechanisms of integrin signaling and the roles of integrins in bone signal transduction, which may give insight into new therapeutic agents to all kinds of skeletal diseases and new strategies for bone tissue engineering.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.
文摘背景:正畸力通过多种信号通路激活牙周组织自噬,进一步增强或减弱相关细胞(牙周膜细胞、骨细胞、破骨细胞和成骨细胞等)的活性来促进牙周重塑。目的:综述目前正畸力介导牙周组织自噬的研究进展和其对正畸牙齿移动的影响。方法:在PubMed、Web of Science、中国生物医学文献数据库和中国知网数据库进行文献检索,设置检索时限为2010-2023年,总结了2010年以来正畸与自噬相关研究进展,最终纳入76篇文献进行分析讨论。结果与结论:(1)正畸力可通过牙周机械感受器和其造成的无菌性炎症引发一系列生物化学信号的转变,进而引起牙周组织自噬。(2)自噬通过级联放大的信号通路如磷脂酰肌醇-3-激酶/蛋白激酶B通路、河马通路及丝裂原活化蛋白激酶通路等,产生相应反馈从而促进牙周组织改建,最终实现牙齿的移动与稳定。正畸力诱导的自噬可差异性调节牙齿压力侧骨吸收和张力侧骨形成,相关靶点在正畸临床治疗的应用中具有良好前景。(3)然而,正畸力与自噬的机制较为复杂,现有研究仅停留在探究自噬对正畸牙齿移动的作用,自噬与正畸牙齿移动过程中的相互调节作用、涉及相关通路上游机械受体及信号通路间的交互作用均需要进一步的探究。
文摘Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli transmitted by integrins influence the cytoskeleton, in turn, the cytoskeleton influences cell adhesion via integrins, then cell adhesion results in a series of signal transduction cascades. In skeleton, integrins also have a key role for bone resoption by osteoclasts and reformation by osteoblasts. In present review, the proteins involved in integrin signal transduction and integrin signal transduction pathways were discussed, mainly on the basic mechanisms of integrin signaling and the roles of integrins in bone signal transduction, which may give insight into new therapeutic agents to all kinds of skeletal diseases and new strategies for bone tissue engineering.