骨溶解
病态的
骨吸收
破骨细胞
医学
癌症研究
吸收
假体周围
膜联蛋白A2
内科学
病理
膜联蛋白
牙科
外科
受体
关节置换术
染色
作者
Hend Alhasan,Mohamad Alaa Terkawi,Gen Matsumae,Taku Ebata,Yuan Tian,Tomohiro Shimizu,Yoshio Nishida,Shunichi Yokota,Fayna García-Martín,Mahmoud M. Abd Elwakil,Daisuke Takahashi,Mahmoud A. Younis,Hideyoshi Harashima,Ken Kadoya,Norimasa Iwasaki
标识
DOI:10.1038/s41467-022-31646-0
摘要
There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.
科研通智能强力驱动
Strongly Powered by AbleSci AI