open access

https://hdl.handle.net/2115/86790

Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis

英語

2022-07-07

Nature Portfolio

Nature communications

13(1)

3919

Periprosthetic osteolysis is a cause of arthroplasty failure without available therapies. Here the authors show that Annexin A1 (AnxA1) is involved in in periprosthetic osteolysis and exerts potential therapeutic effects through suppressing NF kappa B signaling and promoting the PPAR-gamma pathway resulting in inhibition of inflammation and osteoclasts differentiation induced by wear debris. 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 NF kappa B signaling and promoting the PPAR-gamma 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-gamma antagonist, suggesting that the AnxA1/PPAR-gamma axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-alpha and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.

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