Advances in the signaling pathway of M2 macrophages involved in bone regeneration
Zhang Jie1, Tian Ai1, 2
1School of Stomatology, Guizhou Medical University, Guiyang 550001, Guizhou Province, China; 2Department of Restoration and Implant, Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
Abstract: BACKGROUND: Studying the molecular mechanisms of M2 macrophage-induced bone regeneration and collating and analyzing the comprehensive gene regulatory network of multiple signaling pathways are important for targeting and regulating the immune response mediated by bone replacement materials to promote alveolar bone defect repair.
OBJECTIVE: To review relevant literature and summarize the research progress in relevant signaling pathways of M2 macrophages in bone regeneration, in order to find accurate and proactive immunomodulatory strategies for the regenerative treatment of alveolar bone defects in clinical settings.
METHODS: Relevant literature in CNKI, Web of Science and PubMed were searched. Search terms were “macrophages, polarization, bone regeneration, osteogenesis, signaling pathway” in Chinese and English. According to the inclusion criteria, 55 articles were included for review.
RESULTS AND CONCLUSION: The role of macrophages in bone healing is complex, and switching M0/M1 macrophages to the M2 phenotype through a fine-tuned and precise strategy leads to the formation of an appropriate M2 dominance, which is more conducive to bone regeneration. Once the M2 macrophage phenotype is altered, their cell surface markers, secreted cytokines and chemokines, as well as transcriptional and epigenetic pathways (signaling pathways) are changed accordingly. The article summarizes the molecular mechanisms involved in the polarization of M2 macrophages and thus inducing bone defect repair or osteogenic differentiation by various signaling pathways over the past 7 years. Each signaling pathway plays an important role in participating in or regulating the inflammatory response, osteogenesis and chondrogenic differentiation during bone metabolism. Numerous in vivo and ex vivo studies have shown that targeting and modulating signaling pathways may be an effective way to promote bone regeneration by targeting macrophage polarization. Further clinical studies are needed to elucidate whether modulating signaling pathways in favor of reducing the M1/M2 macrophage ratio may be an effective way to promote alveolar bone defect repair. Once this mechanism is clearly elucidated, pharmacology and novel biomaterials targeting the macrophage polarization state may be used as a strategy to promote bone regeneration.
Key words: macrophage polarization, signaling pathway, bone regeneration, osteogenesis, review