摘要
骨骼形成后会处于不断的分解与重建中。通过骨骼形成与骨骼吸收之间的动态平衡来维持骨量。如果二者间的平衡被打破,骨吸收大于骨形成时,骨量会减少,骨骼微环境随之发生改变,脆性增加,进而引发骨质疏松、骨折等疾病。其中,骨骼形成是成骨细胞的重要功能。成骨细胞由间充质干细胞(mesenchymal stem cells,MSCs)分化而来,是骨组织形成的主要功能细胞,其对维持骨骼的完整性有重要作用。骨骼形成过程受到多条信号通路的调控。目前已发现,Wnt/β-catenin、BMP/Smads、MAPK等通路参与成骨细胞的分化及骨骼形成的调节过程。此外,一些信号分子可能也有助于增加成骨细胞的数量或增加血管化,例如生长因子FGF、PDGF和VEGF等。这些通路也是重要的促进骨骼形成的靶点,了解它们潜在的分子机制具有重要意义。本文对上述通路的调控机制及最新研究进展进行归纳和总结,详细阐释了上述信号通路在促进骨骼形成、间充质干细胞及成骨细胞分化等过程中的进展及临床转化应用,以期为临床上寻找新的促进骨骼形成的药物提供理论依据和研究方向。
Postnatal skeletal growth and bone remodeling are highly coordinated processes that are primarily mediated by bone formation and bone resorption.The imbalance in bone formation relative to bone resorption will result in the net bone loss that results in changes of bone microenvironment and increased fragility,leading to diseases such as osteoporosis and bone fracture.Bone formation is mediated by osteoblasts,which mainly derived from mesenchymal stem cells(MSCs).Bone formation process is regulated by multiple signal pathways.It has been found that Wnt/β-catenin,BMP/Smads,MAPK and other pathways are involved in the regulation of osteoblast differentiation and bone formation.In addition,some signaling related molecules may also contribute to the number increase of osteoblasts and enhanced vascularization,such as growth factors FGF,PDGF,and VEGF.These factors have been regarded as targets to promote bone formation,therefore it is important to understand their underlying molecular mechanisms.This review summarizes the latest research progress on regulatory mechanisms and clinical translational application about the above pathways on promoting bone formation,mesenchymal stem cells growth and differentiation,aiming to provide theoretical basis and directions for searching new potential candidate drugs to promote bone formation.
作者
丁祎
崔宇
张令强
DING Yi;CUI Yu;ZHANG Ling-Qiang(Institute of Lifeomics,Academy of Military Medical Sciences,Academy of Military Sciences,State Key Laboratory of Proteomics,Beijing 100850,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2021年第4期428-436,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金青年项目(No.31800746)资助。
关键词
间充质干细胞
成骨细胞
骨骼形成
信号通路
生长因子
mesenchymal stem cell(MSC)
osteoblast
bone formation
signaling pathway
growth factor
