The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease  

作　　者：Mengrui Wu Shali Wu Wei Chen Yi-Ping Li 

机构地区：[1]Department of Cell and Developmental Biology,College of Life Sciences,Zhejiang University,Hangzhou,Zhejiang,China [2]Division in Cellular and Molecular Medicine,Department of Pathology and Laboratory Medicine,Tulane University School of Medicine,Tulane University,New Orleans,LA,USA

出　　处：《Cell Research》2024年第2期101-123,共23页细胞研究（英文版）

基　　金：supported by the National Institutes of Health(AR-070135 and AG-056438 to W.C.,and AR075735,DE023813,and DE028264 to Y.P.L);the National Natural Science Foundation of China(81900806 and 32070814 to M.W);the Qizhen Grant of Zhejiang University(226-2022-00132 to M.W.).

摘　　要：Transforming growth factor-βs (TGF-βs) and bone morphometric proteins (BMPs) belong to the TGF-β superfamily and perform essential functions during osteoblast and chondrocyte lineage commitment and differentiation, skeletal development, and homeostasis. TGF-βs and BMPs transduce signals through SMAD-dependent and -independent pathways;specifically, they recruit different receptor heterotetramers and R-Smad complexes, resulting in unique biological readouts. BMPs promote osteogenesis, osteoclastogenesis, and chondrogenesis at all differentiation stages, while TGF-βs play different roles in a stage-dependent manner. BMPs and TGF-β have opposite functions in articular cartilage homeostasis. Moreover, TGF-β has a specific role in maintaining the osteocyte network. The precise activation of BMP and TGF-β signaling requires regulatory machinery at multiple levels, including latency control in the matrix, extracellular antagonists, ubiquitination and phosphorylation in the cytoplasm, nucleus-cytoplasm transportation, and transcriptional co-regulation in the nuclei. This review weaves the background information with the latest advances in the signaling facilitated by TGF-βs and BMPs, and the advanced understanding of their diverse physiological functions and regulations. This review also summarizes the human diseases and mouse models associated with disordered TGF-β and BMP signaling. A more precise understanding of the BMP and TGF-β signaling could facilitate the development of bona fide clinical applications in treating bone and cartilage disorders.

关 键 词：HOMEOSTASIS CARTILAGE PRECISE 

分 类 号：R68[医药卫生—骨科学]