Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in frag...Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.展开更多
Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide.Changed bone metabolism is one of the important long-term complications associated with diabetes mellitu...Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide.Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus.Alveolar bone loss is one of the main outcomes of periodontitis,and diabetes is among the primary risk factors for periodontal disease.In this review,we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects,focusing on alveolar bone loss.Bone remodelling begins with osteoclasts resorbing bone,followed by new bone formation by osteoblasts in the resorption lacunae.Therefore,we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.展开更多
Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and b...Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).展开更多
The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,w...The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.展开更多
文摘Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.
基金funded by the National Institute of Dental and Craniofacial Research(grant no. DE021921)
文摘Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide.Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus.Alveolar bone loss is one of the main outcomes of periodontitis,and diabetes is among the primary risk factors for periodontal disease.In this review,we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects,focusing on alveolar bone loss.Bone remodelling begins with osteoclasts resorbing bone,followed by new bone formation by osteoblasts in the resorption lacunae.Therefore,we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.
基金This work was supported by the National Key Research Program of China(No.2006CB944007,to DJL)the National Natural Science Foundation of China(No.30801502,to LW)+1 种基金the Shanghai Leading Academic Discipline Project B117(to DJL)the Program for Outstanding Medical Academic Leaders(to DJL).
文摘Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).
基金supported by an intramural research programme,NHGRI,National Institutes of Health(NIH)the National Science Foundation for Excellent Young Scholars of China(grant no.813220170)+1 种基金the Innovation Team of Sichuan Province(2015TD0011)the China Scholarship Council
文摘The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.
