Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5.

Excessive mechanical stress is a major cause of knee osteoarthritis. However, the mechanism by which the mechanical stress begets osteoarthritis development remains elusive. Hydrogen peroxide-inducible clone-5 (Hic-5; TGFβ1i1), a TGF-β inducible focal adhesion adaptor, has previously been reported as a mediator of mechanotransduction. In this study, we analyzed the in vivo function of Hic-5 in development of osteoarthritis, and found that mice lacking Hic-5 showed a significant reduction in development of osteoarthritis in the knee. Furthermore, we found reduced expression of catabolic genes, such as metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 in osteoarthritic lesions in mice lacking Hic-5. During osteoarthritis development, Hic-5 is detected in chondrocytes of articular cartilage. To investigate the role of Hic-5 in chondrocytes, we isolated chondrocytes from articular cartilage of wild type and Hic-5-deficient mice. In these primary cultured chondrocytes, Hic-5 deficiency resulted in suppression of catabolic gene expression induced by osteoarthritis-related cytokines such as tumor necrosis factor α and interleukin 1β. Furthermore, Hic-5 deficiency in chondrocytes suppressed catabolic gene expression induced by mechanical stress. Revealing the regulation of chondrocyte catabolism by Hic-5 contributes to understanding the pathophysiology of osteoarthritis induced by mechanical stress.

Citation

Aya Miyauchi, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Song Ho Chang, Taku Saito, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki. Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5. Scientific reports. 2019 Oct 31;9(1):15770

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PMID: 31673109

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