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

Hend Alhasan, Mohamad Alaa Terkawi (), Gen Matsumae, Taku Ebata, Yuan Tian, Tomohiro Shimizu (), Yoshio Nishida, Shunichi Yokota, Fayna Garcia-Martin, Mahmoud M. Abd Elwakil, Daisuke Takahashi, Mahmoud A. Younis, Hideyoshi Harashima, Ken Kadoya and Norimasa Iwasaki
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Hend Alhasan: Hokkaido University
Mohamad Alaa Terkawi: Hokkaido University
Gen Matsumae: Hokkaido University
Taku Ebata: Hokkaido University
Yuan Tian: Hokkaido University
Tomohiro Shimizu: Hokkaido University
Yoshio Nishida: Hokkaido University
Shunichi Yokota: Hokkaido University
Fayna Garcia-Martin: Hokkaido University
Mahmoud M. Abd Elwakil: Hokkaido University
Daisuke Takahashi: Hokkaido University
Mahmoud A. Younis: Hokkaido University
Hideyoshi Harashima: Hokkaido University
Ken Kadoya: Hokkaido University
Norimasa Iwasaki: Hokkaido University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31646-0

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