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
自噬广泛存在于真核细胞中,是细胞基本的自我保护机制。破骨细胞是髓系来源的高度分化的多核巨细胞,具有多种生物学功能。在成骨细胞和骨细胞分泌的巨噬细胞集落刺激因子和RANKL(receptor activator of NF-κB ligand)的作用下,可促进...自噬广泛存在于真核细胞中,是细胞基本的自我保护机制。破骨细胞是髓系来源的高度分化的多核巨细胞,具有多种生物学功能。在成骨细胞和骨细胞分泌的巨噬细胞集落刺激因子和RANKL(receptor activator of NF-κB ligand)的作用下,可促进破骨细胞的形成,对调控和维持骨骼正常代谢发挥作用。自噬作为保守的维持细胞稳态的重要作用机制,同样在骨细胞的形成和功能发挥过程中起着重要的作用。本文旨在总结破骨细胞的生物学作用,概括自噬对破骨细胞的形成及对其生物学作用的调控机制,并对自噬异常造成的骨相关疾病进行总结。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.
文摘自噬广泛存在于真核细胞中,是细胞基本的自我保护机制。破骨细胞是髓系来源的高度分化的多核巨细胞,具有多种生物学功能。在成骨细胞和骨细胞分泌的巨噬细胞集落刺激因子和RANKL(receptor activator of NF-κB ligand)的作用下,可促进破骨细胞的形成,对调控和维持骨骼正常代谢发挥作用。自噬作为保守的维持细胞稳态的重要作用机制,同样在骨细胞的形成和功能发挥过程中起着重要的作用。本文旨在总结破骨细胞的生物学作用,概括自噬对破骨细胞的形成及对其生物学作用的调控机制,并对自噬异常造成的骨相关疾病进行总结。
