Recent research has brought about a clear understanding that successful fracture healing is based on carefully coordinated cross-talk between inflammatory and bone forming cells. In particular, the key role that macrophages play in the recruitment and regulation of the differentiation of mesenchymal stem cells (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies have comprehensively demonstrated that fractures do not heal without the direct involvement of macrophages. Yet the exact mechanisms by which macrophages contribute to bone regeneration remain to be elucidated. Macrophage-derived paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles; however the relative importance of inflammatory (M1) and tissue regenerative (M2) macrophages in guiding MSC differentiation along the osteogenic pathway remains poorly understood. In this review, we summarize the current understanding of the interaction of macrophages and MSCs during bone regeneration, with the emphasis on the role of macrophages in regulating bone formation. The potential implications of aging to this cellular cross-talk are reviewed. Emerging treatment options to improve facture healing by utilizing or targeting MSC-macrophage crosstalk are also discussed.

中文翻译：

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间充质干细胞-巨噬细胞串扰和骨愈合。

最近的研究使人们清楚地了解成功的骨折愈合是基于炎症细胞与骨形成细胞之间精心协调的串扰。特别地，巨噬细胞在骨骼再生期间在募集和调节间充质干细胞（MSC）分化中发挥的关键作用已引起人们的关注。实际上，动物研究已全面证明，如果没有巨噬细胞的直接参与，骨折就无法愈合。然而，仍然需要阐明巨噬细胞促进骨骼再生的确切机制。巨噬细胞衍生的旁分泌信号分子，如制瘤素M，前列腺素E2（PGE2）和骨形态发生蛋白2（BMP2）已显示出关键的作用。然而，炎症（M1）和组织再生（M2）巨噬细胞在引导成骨途径分化为MSC方面的相对重要性仍然知之甚少。在这篇综述中，我们总结了对巨噬细胞和MSC在骨再生过程中相互作用的当前理解，重点是巨噬细胞在调节骨形成中的作用。老化对这种细胞串扰的潜在影响进行了审查。还讨论了通过利用或靶向MSC巨噬细胞串扰来改善骨折愈合的新兴治疗选择。强调巨噬细胞在调节骨形成中的作用。老化对这种细胞串扰的潜在影响进行了审查。还讨论了通过利用或靶向MSC巨噬细胞串扰来改善骨折愈合的新兴治疗选择。强调巨噬细胞在调节骨形成中的作用。老化对这种细胞串扰的潜在影响进行了审查。还讨论了通过利用或靶向MSC巨噬细胞串扰来改善骨折愈合的新兴治疗选择。