| First Author | Zhen G | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 1706 |
| PubMed ID | 33731712 | Mgi Jnum | J:304996 |
| Mgi Id | MGI:6515214 | Doi | 10.1038/s41467-021-21948-0 |
| Citation | Zhen G, et al. (2021) Mechanical stress determines the configuration of TGFbeta activation in articular cartilage. Nat Commun 12(1):1706 |
| abstractText | Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFbeta) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFbeta activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFbeta disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers alphaV integrin-mediated TGFbeta activation. Knockout of alphaV integrin in chondrocytes reversed the alteration of TGFbeta activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFbeta activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis. |
