The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease
Wu, Wu, Chen, Li (2024) The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease Cell Res (IF: 28.1) 34(2) 101-123
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Abstract
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.© 2024. The Author(s).
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837209http://www.ncbi.nlm.nih.gov/pubmed/38267638
http://dx.doi.org/10.1038/s41422-023-00918-9
