The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenes...The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.展开更多
Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommoda...Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis;skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.展开更多
Intervertebral disc degeneration(IVDD)is one of the leading causes of lower back pain,typically accompanied by oxidative stress,inflammatory responses,and imbalances in the mechanical microenvironment.In this study,we...Intervertebral disc degeneration(IVDD)is one of the leading causes of lower back pain,typically accompanied by oxidative stress,inflammatory responses,and imbalances in the mechanical microenvironment.In this study,we developed a multifunctional nanocomposite hydrogel for minimally invasive treatment of IVDD.This hydrogel(TP-Arg@MTG)incorporates tea polyphenol and L-arginine self-assembled nanoparticles(TP-Arg)into a gelatin–mucin matrix,followed by enzymatic crosslinking via transglutaminase to enhance structural stability.The nanoparticles of TP-Arg not only exhibit an exceptional ability to scavenge reactive oxygen species(ROS)but also effectively promote the synthesis of the extracellular matrix(ECM)through nitric oxide(NO)-mediated signaling pathways.Their integration significantly improves the mechanical strength of the hydrogel while enabling sustained release functionality.Gelatin offers cell adhesion and ECM-like architecture,whereas mucin enhances lubrication and moisture retention,better mimicking the native microenvironment of the nucleus pulposus.In vitro and in vivo experiments demonstrate that the hydrogel possesses favorable biocompatibility,effectively attenuates inflammatory responses in nucleus pulposus cells(NPCs),and maintains cellular viability and ECM stability.Collectively,TP-Arg@MTG holds great promise as a novel therapeutic strategy for IVDD by synergistically addressing oxidative damage and mechanical instability through antioxidation,tissue repair promotion,and mechanical reinforcement.展开更多
基金supported in part by grants from 973 Program from the Chinese Ministry of Science and Technology (MOST) (2014CB964704 and 2015CB964503)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB19000000)the National Natural Science Foundation of China (NSFC) (31371463, 81672119, and 81725010)
文摘The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.
基金supported by the National Natural Science Foundation of China(NSFC)[81725010,81672119,81991512,82102554]the Strategic Priority Research Program of the Chinese Academy of Sciences[Grant No.XDB19000000]the Space Medical Experiment Project of China Manned Space Program[HYZHXM01025].
文摘Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis;skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.
基金financial support from the National Natural Science Foundation of China(Nos.82472488,22472042,and 21603166)Xie Ying Program(No.KT20231006133328780)+6 种基金Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents(No.KT20230315104216600)High-level Innovation Team of Wenzhou’s“Ouyue Talent Plan”(No.2024R3003)Scientific Research Startup Fund of Wenzhou Institute,University of Chinese Academy of Sciences(No.WIUCASQD2019001)the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2023C03084)Zhejiang Provincial Science and Technology Project for Public Welfare(No.LQ24H090010)the Research Center of Clinical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province(No.WIBEK181006)Major Science and Technology Project of Wenzhou Science and Technology(No.ZG2022017).
文摘Intervertebral disc degeneration(IVDD)is one of the leading causes of lower back pain,typically accompanied by oxidative stress,inflammatory responses,and imbalances in the mechanical microenvironment.In this study,we developed a multifunctional nanocomposite hydrogel for minimally invasive treatment of IVDD.This hydrogel(TP-Arg@MTG)incorporates tea polyphenol and L-arginine self-assembled nanoparticles(TP-Arg)into a gelatin–mucin matrix,followed by enzymatic crosslinking via transglutaminase to enhance structural stability.The nanoparticles of TP-Arg not only exhibit an exceptional ability to scavenge reactive oxygen species(ROS)but also effectively promote the synthesis of the extracellular matrix(ECM)through nitric oxide(NO)-mediated signaling pathways.Their integration significantly improves the mechanical strength of the hydrogel while enabling sustained release functionality.Gelatin offers cell adhesion and ECM-like architecture,whereas mucin enhances lubrication and moisture retention,better mimicking the native microenvironment of the nucleus pulposus.In vitro and in vivo experiments demonstrate that the hydrogel possesses favorable biocompatibility,effectively attenuates inflammatory responses in nucleus pulposus cells(NPCs),and maintains cellular viability and ECM stability.Collectively,TP-Arg@MTG holds great promise as a novel therapeutic strategy for IVDD by synergistically addressing oxidative damage and mechanical instability through antioxidation,tissue repair promotion,and mechanical reinforcement.
