2023-08-04 デラウェア大学 (UD)
◆健康な軟骨細胞にはアドセベリンが多く含まれ、これが細胞の構造を保護する役割を果たします。アクチン結合(F-actin)と呼ばれる細胞の構造を支持する要素との関連も初めて明らかにされました。
◆F-actinが失われると細胞が死滅し、関節の悪化を引き起こします。adseverinを保つことで細胞の生存を確保できる可能性があり、変形性関節症の治療法に新たな展望をもたらす研究とされています。今後はこのタンパク質をターゲットにした治療法の開発が進む可能性があります。
<関連情報>
- https://www.udel.edu/udaily/2023/august/osteoarthritis-research-protein-healthy-cartilage-justin-parreno/
- https://www.science.org/doi/full/10.1126/sciadv.adf1130
アクチン結合タンパク質アドセベリンが肥大軟骨細胞の分化と変形性関節症の進行を調節する Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression
Byron Chan,Michael Glogauer,Yongqiang Wang,Jeffrey Wrana,Kin Chan,Frank Beier,Supinder Bali,Boris Hinz,Justin Parreno,Sajjad Ashraf, and Rita Kandel
Science Advances Published:4 Aug 2023
DOI:https://doi.org/10.1126/sciadv.adf1130
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.
