The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can b...The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can be harnessed to promote diabetic wound healing remains unexplored.Here,we investigate the impact of a bone injury strategy on diabetic wound healing,leveraging the body’s innate regenerative capacity to stimulate osteokine release and influence remote skin wound repair.This study demonstrates that the tibial defect significantly accelerates ipsilateral diabetic foot skin wound healing.Mechanistically,we identify osteokines,platelet-derived growth factor-BB(PDGF-BB),as the key to initiating this process.Bone defect triggers a substantial release of PDGF-BB,which reaches the skin wound site via peripheral circulation.At the skin wound site,PDGF-BB mediates the secretion of keratinocyte growth factor(KGF)from fibroblasts via the PDGFRβsignaling pathway,thereby promoting the rapid re-epithelialization of epidermal cells through a paracrine pathway.Additionally,elevated PDGF-BB levels enhance the regeneration of CD31hi Emcnhi blood vessels within the wound.展开更多
The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can b...The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can be harnessed to promote diabetic wound healing remains unexplored.Here,we investigate the impact of a bone injury strategy on diabetic wound healing,leveraging the body's innate regenerative capacity to stimulate osteokine release and influence remote skin wound repair.This study demonstrates that the tibial defect significantly accelerates ipsilateral diabetic foot skin wound healing.Mechanistically,we identify osteokines,platelet-derived growth factor-BB(PDGF-BB),as the key to initiating this process.Bone defect triggers a substantial release of PDGF-BB,which reaches the skin wound site via peripheral circulation.At the skin wound site,PDGF-BB mediates the secretion of keratinocyte growth factor(KGF)from fibroblasts via the PDGFRβsignaling pathway,thereby promoting the rapid reepithelialization of epidermal cells through a paracrine pathway.Additionally,elevated PDGF-BB levels enhance the regeneration of CD31^(h i)Emcn^(h i)blood vessels within the wound.Importantly,we demonstrate the therapeutic potential of osteokines by showing that a collagen hydrogel loaded with osteokines promotes wound healing in diabetic mice.Our findings reveal a clear link between bone and skin wound healing,providing a therapeutic inspiration for chronic wounds that are difficult to treat locally.展开更多
In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). T...In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles(EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.展开更多
Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-...Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.展开更多
Bone has long been considered as a silent organ that provides a reservoir of calcium and phosphorus,traditionally.Recently,further study of bone has revealed additional functions as an endocrine organ connecting syste...Bone has long been considered as a silent organ that provides a reservoir of calcium and phosphorus,traditionally.Recently,further study of bone has revealed additional functions as an endocrine organ connecting systemic organs of the whole body.Communication between bone and other organs participates in most physiological and pathological events and is responsible for the maintenance of homeostasis.Here,we present an overview of the crosstalk between bone and other organs.Furthermore,we describe the factors mediating the cross-talk and review the mechanisms in the development of potential associated diseases.These connections shed new light on the pathogenesis of systemic diseases and provide novel potential targets for the treatment of systemic diseases.展开更多
基金supported by the Key Program of the National Natural Science Foundation of China grants 32230059the Basic Science Center Program T2288102+1 种基金the National Natural Science Foundation of China grants 32301123the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry JKVD1211002.
文摘The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can be harnessed to promote diabetic wound healing remains unexplored.Here,we investigate the impact of a bone injury strategy on diabetic wound healing,leveraging the body’s innate regenerative capacity to stimulate osteokine release and influence remote skin wound repair.This study demonstrates that the tibial defect significantly accelerates ipsilateral diabetic foot skin wound healing.Mechanistically,we identify osteokines,platelet-derived growth factor-BB(PDGF-BB),as the key to initiating this process.Bone defect triggers a substantial release of PDGF-BB,which reaches the skin wound site via peripheral circulation.At the skin wound site,PDGF-BB mediates the secretion of keratinocyte growth factor(KGF)from fibroblasts via the PDGFRβsignaling pathway,thereby promoting the rapid re-epithelialization of epidermal cells through a paracrine pathway.Additionally,elevated PDGF-BB levels enhance the regeneration of CD31hi Emcnhi blood vessels within the wound.
基金supported by the Key Program of the National Natural Science Foundation of China grants 32230059the Basic Science Center Program T2288102,the National Natural Science Foundation of China grants 32301123the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry JKVD1211002。
文摘The treatment of severe diabetic foot remains a clinical challenge.While it is established that bone can exert systemic effects through the secretion of osteokines on other organs,whether this endocrine function can be harnessed to promote diabetic wound healing remains unexplored.Here,we investigate the impact of a bone injury strategy on diabetic wound healing,leveraging the body's innate regenerative capacity to stimulate osteokine release and influence remote skin wound repair.This study demonstrates that the tibial defect significantly accelerates ipsilateral diabetic foot skin wound healing.Mechanistically,we identify osteokines,platelet-derived growth factor-BB(PDGF-BB),as the key to initiating this process.Bone defect triggers a substantial release of PDGF-BB,which reaches the skin wound site via peripheral circulation.At the skin wound site,PDGF-BB mediates the secretion of keratinocyte growth factor(KGF)from fibroblasts via the PDGFRβsignaling pathway,thereby promoting the rapid reepithelialization of epidermal cells through a paracrine pathway.Additionally,elevated PDGF-BB levels enhance the regeneration of CD31^(h i)Emcn^(h i)blood vessels within the wound.Importantly,we demonstrate the therapeutic potential of osteokines by showing that a collagen hydrogel loaded with osteokines promotes wound healing in diabetic mice.Our findings reveal a clear link between bone and skin wound healing,providing a therapeutic inspiration for chronic wounds that are difficult to treat locally.
基金supported by the National Natural Science Foundation of China (82230071, 82172098)the Integrated Project of Major Research Plan of National Natural Science Foundation of China (92249303)+2 种基金the Laboratory Animal Research Project of Shanghai Committee of Science and Technology (23141900600)the Shanghai Clinical Research Plan (SHDC2023CRT01)the Young Elite Scientist Sponsorship Program by China Association for Science and Technology (YESS20230049)。
文摘In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles(EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.
文摘Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.
基金supported by the National key research and development program(2020YFC2009004,2021YFC2501700)National Natural Science Foundation of China(81874010)and PKU-Baidu Fund(2020BD014).
文摘Bone has long been considered as a silent organ that provides a reservoir of calcium and phosphorus,traditionally.Recently,further study of bone has revealed additional functions as an endocrine organ connecting systemic organs of the whole body.Communication between bone and other organs participates in most physiological and pathological events and is responsible for the maintenance of homeostasis.Here,we present an overview of the crosstalk between bone and other organs.Furthermore,we describe the factors mediating the cross-talk and review the mechanisms in the development of potential associated diseases.These connections shed new light on the pathogenesis of systemic diseases and provide novel potential targets for the treatment of systemic diseases.
