2022, Vol. 26 ›› Issue (33): 5384-5392

Molecular mechanism of magnesium ion promoting bone regeneration

Zhang Jingxin1, Liu Linfeng1, Zhang Shiwen2, Lin Jie2   

Abstract: BACKGROUND: In recent years, the role of magnesium ion in promoting bone regeneration has been widely recognized in experiment and clinic. Magnesium materials are widely used in bone regeneration. The molecular mechanism of magnesium promoting bone regeneration involves a variety of cells and cytokines in the local environment of bone, but it has not been fully clarified.
OBJECTIVE: To review the molecular mechanism of magnesium ion on promoting bone regeneration.
METHODS: The PubMed, CNKI and Wanfang databases were searched for relevant articles with the key words of “magnesium OR magnesium ion”, “bone regeneration OR bone repair OR bone repairing OR osteogenesis OR osteanagenesis OR osteanaphysis OR osteoanagenesis”, “mechanism OR molecular mechanism OR cell mechanism OR signal pathway OR signaling pathway OR endothelial cell OR vascular OR immune” in English and Chinese, respectively. The search time was from database establishment to December 2021. According to the exclusion and inclusion criteria, 81 articles were included for review.
RESULTS AND CONCLUSION: (1) For mesenchymal stem cells, magnesium ion can significantly promote their proliferation, migration, adhesion and osteogenic differentiation. In particular, it can not only directly promote their osteogenic differentiation through the classical Wnt pathway and MAPK/ERK pathway, but also indirectly promote their osteogenic differentiation by promoting the secretion of CGRP by ganglion cells and bone morphogenetic protein by macrophages. (2) For osteoblasts, magnesium ion mainly promotes their proliferation, migration, adhesion, osteogenic activity and inhibits their apoptosis through TRPM/PI3K signaling pathway. (3) For osteoclasts, magnesium ion inhibits osteoclast formation and bone resorption mainly through nuclear factor-κB signaling pathway. (4) Magnesium ion regulates the immune response in the bone environment, transforms the phenotype of macrophages, promotes the secretion of bone factors, and reduces the secretion of inflammatory factors, thereby reducing the inflammatory response. Simultaneously, magnesium ion promotes the proliferation, migration, adhesion and angiogenesis of vascular endothelial cells, thereby contributing to angiogenesis. (5) The role of magnesium ion in promoting bone regeneration has rich molecular mechanisms. The molecular mechanism that magnesium ions can improve the microenvironment of bone regeneration by regulating immune response and angiogenesis has become a research hotspot in recent years, especially the role of macrophage nuclear factor κB pathway and H-type vascular endothelial cells on bone regeneration, which jointly created a good microenvironment for bone regeneration. (6) Although the molecular mechanism is rich, a lot of researches are still needed to further clarify the molecular mechanism of immune regulation and pro-angiogenesis on bone regeneration and the appropriate concentration of magnesium ion on promoting bone regeneration.
Key words: magnesium ion, magnesium, bone regeneration, bone repair, bone defect, bone remodeling, molecular mechanism, biomaterial, tissue engineering