Pak4-mediated crosstalk between necroptotic macrophages and tendon stem/progenitor cells contributes to traumatic heterotopic ossification formation.

ABSTRACT: The formation of traumatic heterotopic ossification (HO) is an abnormal repair process after soft tissue injury. Recent studies establish the involvement of immune cells and cellular metabolism in the tissue healing process; however, their role in HO remains unknown. Here, by using murine burn/tenotomy model in vivo and tendon stem/progenitor cells (TSPCs) osteogenic differentiation model in vitro, together with techniques including transgenic knockout, gene knockdown, transcriptome and proteome sequencings, mass spectrometry, co-immunoprecipitation, seahorse, etc., we reveal a novel p21-activated kinase 4 (Pak4) mediated crosstalk where the necroptotic macrophages arouse TSPCs with reduced fatty acid β-oxidation (FAO), to promote aberrant osteogenic differentiation during HO formation. Ne

SUBMITTER: Sun Z 

PROVIDER: S-EPMC12536042 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature