Volume 34, No 2, Feb 2024

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 34 Issue 2, February 2024: 101-123   |  Open Access

REVIEW ARTICLE

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

Mengrui Wu^1,* , Shali Wu¹ , Wei Chen² , Yi-Ping Li^2,*

¹Department of Cell and Developmental Biology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China
²Division in Cellular and Molecular Medicine, Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, Tulane University, New Orleans, LA, USA
Correspondence: Mengrui Wu(mengruiwu@zju.edu.cn)Yi-Ping Li(yli81@tulane.edu)

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.

https://doi.org/10.1038/s41422-023-00918-9

FULL TEXT | PDF

Browse 115