POSTN‐Mediated Interplay of M1 Polarized Macrophage with Tendon‐Derived Stem Cells to Drive Traumatic Heterotopic Ossification Formation through PTK7/ATK Signaling?

Abstract Tendinous heterotopic ossification can cause pain and restricted joint mobility in affected areas, and it is a common and severe complication following tendon injuries. This condition significantly reduces the postoperative quality of life of patients, and its incidence is increasing year by year. Due to the unclear pathogenesis, there are currently no effective treatment methods. Although recent studies suggest that macrophages affect the process of traumatic heterotopic ossification (HO) in mice, their role in HO still requires further clarification. Here, it is disclosed that the formation of trauma‐induced HO is accompanied by the polarization of macrophages toward the M1 phenotype. Additionally, secretion containing periostin (POSTN) that is secreted by M1 macrophages reduces fatty acid β – oxidation in tendon‐derived stem cells (TDSCs) and facilitates the formation of heterotopic bone. Mechanistically, M1 macrophages release POSTN during the HO process, which directly binds to PTK7 in TDSCs, thereby increasing AKT phosphorylation at the S124 site and initiating osteogenic differentiation. This study demonstrates the role of M1 macrophages and their secreted POSTN in traumatic heterotopic ossification, highlighting the potential of POSTN as a therapeutic target for HO.