Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo, 060-8638, Japan.
Graduate School and Faculty of Advanced Life Science, Laboratory of Advanced Chemical Biology, Hokkaido University, N21 W11, Kita-21, Nish-11, Kita-ku, Sapporo, 001-0021, Japan.
Nat Commun. 2022 Jul 7;13(1):3919. doi: 10.1038/s41467-022-31646-0.
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.
目前，对于假体周围骨溶解，即最常见的关节置换失败原因，尚无有效的治疗方法。本研究旨在探讨 Annexin A1（AnxA1）在假体周围骨溶解中的作用及其潜在的治疗方法。研究发现，减少颅骨组织中 AnxA1 的表达与骨溶解病变的增加有关，并且在 AnxA1 缺陷型小鼠中，植入碎片诱导的骨溶解病变比野生型小鼠更为严重。AnxA1 通过抑制 NFκB 信号通路和促进 PPAR-γ 通路来抑制破骨细胞的分化。将 N 端-AnxA1（Ac2-26 肽）施用于颅骨可显著减轻由磨损碎片引发的骨溶解病变。在接受 PPAR-γ 拮抗剂的小鼠中，这些治疗效果被消除，这表明 AnxA1/PPAR-γ 轴在骨溶解中具有抑制作用。Ac2-26 的给药抑制了 TNF-α 和 RANKL 注射诱导的小鼠骨溶解。这些发现表明 AnxA1 是治疗假体周围骨溶解的潜在治疗剂。
