Myeloid cells are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by myeloid cells on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal myeloid cells, primarily the M2 macrophages during bone regeneration. Knockout of periostin in myeloid cells reduces cortical bone thickness, disrupts trabecular bone connectivity, impairs repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation is a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β), it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in myeloid cells by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our findings suggest that mechanical stimulation regulates periostin expression and promotes M2 macrophage polarization, highlighting the potential of mechanically conditioned macrophages as a therapeutic strategy for enhancing bone repair.

髓系细胞在骨折修复的炎症和重塑阶段起着关键作用。在这里，我们研究了骨髓细胞表达的骨膜蛋白对单皮质胫骨缺损 （MTD） 模型中骨再生的影响。在这项研究中，我们表明骨膜蛋白由骨膜骨髓细胞表达，主要是骨再生过程中的 M2 巨噬细胞。髓系细胞中骨膜蛋白的敲除降低了皮质骨厚度，破坏了小梁骨连接，损害了修复损伤，并阻碍了 M2 巨噬细胞极化。机械刺激是巨噬细胞中 periostin 的调节剂。通过激活转化生长因子-β （TGF-β），它增加巨噬细胞中骨膜蛋白的表达并诱导 M2 极化。这种机械敏感效应还通过加强血管生成-成骨耦合来逆转髓系细胞中骨膜蛋白缺乏诱导的延迟骨修复。此外，通过骨缺损将机械调节的巨噬细胞移植到骨膜中可显著增强修复，证实了巨噬细胞分泌的骨膜蛋白在骨修复中的关键作用。总之，我们的研究结果表明，机械刺激调节骨膜蛋白表达并促进 M2 巨噬细胞极化，突出了机械调节巨噬细胞作为增强骨修复的治疗策略的潜力。