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The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease
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The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease
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Journal Article
The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease
2024
Overview
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.
Publisher
Springer Nature Singapore,Nature Publishing Group
Subject
/ 13/51
/ 631/136
/ 631/80
/ 64
/ 82
/ 96
/ Animals
/ Biomedical and Life Sciences
/ Dwarfism
/ Humans
/ Knee
/ Latency
/ Ligands
/ Mice
/ Nuclei
/ Regulatory mechanisms (biology)
/ Review
/ Transforming Growth Factor beta - metabolism
