Oncostatin M regulates macrophages polarization in osseointegration via yes-associated protein

Abstract

ObjectivesOncostatin M(OSM), secreted by monocytes and macrophages, has been noted to participate in bone homeostasis and macrophage polarization, which might be regulated by yes-associated protein (YAP). This study aimed to elucidate the influence and mechanisms of OSM-YAP on macrophages polarization in osseointegration. Material and methodsIn vitro, flow cytometry, real-time PCR, and Elisa were performed to evaluate inflammatory function in bone marrow-derived macrophages (BMDMs) with OSM, siOSMR, and YAP inhibitor verteporfin (VP). In vivo, macrophage-specific YAP-deficient mice were generated to investigate the role of OSM via YAP signaling in osseointegration. ResultsThis study demonstrated that OSM could inhibit the M1 polarization, promote the M2 polarization, and induce the expression of osteogenic-related factors via VP. The conditional knock-out of YAP inhibited the osseointegration in mice, and promoted the inflammatory reaction around the implants, while OSM could restore the effect. ConclusionsOur results demonstrated that OSM might play an important role in the polarization of BMDMs, and bone formation around dental and femoral implants. This effect was closely conducted by Hippo-YAP pathway. Clinical SignificanceUnderstanding the role and mechanism of OSM in macrophage polarization around dental implants could improve comprehension of signal network of osseointegration, and it might offer a potential target of therapies to accelerate osseointegration and reduce inflammatory reactions.