Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression
Date
2023-08-04
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Publisher
Science Advances
Abstract
In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin−/−) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin−/− mice who underwent surgical induction of OA. Adseverin−/− chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.
Description
This article was originally published in Science Advances. The version of record is available at: https://doi.org/10.1126/sciadv.adf1130. Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
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Citation
Byron Chan et al. ,Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression.Sci. Adv.9,eadf1130(2023).DOI:10.1126/sciadv.adf1130