Frade Bianca Braga, Dias Rhayra Braga, Gemini Piperni Sara, Bonfim Danielle Cabral
Laboratory of Stem Cells and Bone Regeneration, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Postgraduation Program in Biological Sciences-Biophysics, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Stem Cell Investig. 2023 Feb 8;10:4. doi: 10.21037/sci-2022-038. eCollection 2023.
This review addresses the latest advances in research on the role of macrophages in fracture healing, exploring their relationship with failures in bone consolidation and the perspectives for the development of advanced and innovative therapies to promote bone regeneration.
The bone can fully restore its form and function after a fracture. However, the regenerative process of fracture healing is complex and is influenced by several factors, including macrophage activity. These cells have been found in the fracture site at all stages of bone regeneration, and their general depletion or the knockdown of receptors that mediate their differentiation, polarization, and/or function result in impaired fracture healing.
The literature search was carried out in the PubMed database, using combinations of the keywords "macrophage", "fracture healing, "bone regeneration", and "bone repair". Articles published within the last years (2017-2022) reporting evidence from long bone fracture healing experiments were included.
Studies published in the last five years on the role of macrophages in fracture healing strengthened the idea that what appears to be essential when it comes to a successful consolidation is the right balance between the M1/M2 populations, which have different but complementary roles in the process. These findings opened promising new avenues for the development of several macrophage-targeted therapies, including the administration of molecules and/or biomaterials intended to regulate macrophage differentiation and polarization, the local transplantation of macrophage precursors, and the use of exosomes to deliver signaling molecules that influence macrophage activities. However, more research is still warranted to better understand the diversity of macrophage phenotypes and their specific roles in each step of fracture healing and to decipher the key molecular mechanisms involved in the crosstalk between macrophages and other microenvironmental cell types, such as endothelial and skeletal stem/progenitor cells.
本综述阐述了巨噬细胞在骨折愈合中作用的最新研究进展，探讨了它们与骨愈合失败的关系以及促进骨再生的先进创新疗法的发展前景。
骨折后骨骼能够完全恢复其形态和功能。然而，骨折愈合的再生过程复杂，受多种因素影响，包括巨噬细胞活性。在骨再生的各个阶段，这些细胞都存在于骨折部位，其总体耗竭或介导其分化、极化和/或功能的受体敲低会导致骨折愈合受损。
在PubMed数据库中进行文献检索，使用“巨噬细胞”“骨折愈合”“骨再生”和“骨修复”等关键词组合。纳入过去几年（2017 - 2022年）发表的报道长骨骨折愈合实验证据的文章。
过去五年发表的关于巨噬细胞在骨折愈合中作用的研究强化了这样一种观点，即在成功愈合方面，关键似乎是M1/M2群体之间的正确平衡，它们在这个过程中具有不同但互补的作用。这些发现为开发多种巨噬细胞靶向疗法开辟了有前景的新途径，包括给予旨在调节巨噬细胞分化和极化的分子和/或生物材料、巨噬细胞前体的局部移植以及使用外泌体传递影响巨噬细胞活性的信号分子。然而，仍需要更多研究来更好地理解巨噬细胞表型的多样性及其在骨折愈合每个步骤中的具体作用，并破译巨噬细胞与其他微环境细胞类型（如内皮细胞和骨骼干/祖细胞）之间相互作用的关键分子机制。
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