Mechanism of dna methylation in exercise intervention for osteoporosis / 中国组织工程研究

ABSTRACT

BACKGROUND: The dynamic balance between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts is the basis for maintaining the stability of the body’s bone tissue. The metabolic imbalance between them can cause bone loss and fine structure degeneration of the bone cells, leading to osteoporosis. OBJECTIVE: To review the role of DNA methylation in osteoporosis and to explore the mechanism of exercise affecting DNA methylation and DNA methylation regulating bone metabolism. METHODS: A computer-based search of PubMed and CNKI databases was performed for relevant articles published from January 2002 to April 2020 with “DNA methylation; Osteoporosis; Exercise intervention; Mechanical stress; Osteogenic differentiation” as key words in English and Chinese, respectively. Initially, finally 52 eligible articles were included for result analysis. RESULTS AND CONCLUSION: DNA methylation is a relatively conservative and stable apparent modification, which regulates gene expression, silencing and disease occurrence. Studies have shown that reduced methylation levels of genes such as β-catenin, Runx2, osteopontin (OPG) can promote their expression and activate Wnt Pathway, whereas the reduction of methylation level of Sclerosin, receptor activator of nuclear factor kappa B ligand (RANKL) and other genes can promote their expression, and inhibit Wnt pathway and reduce the ratio of OPG/RANKL, thereby affecting the proliferation, differentiation and function of osteoblasts and osteoclasts, and accordingly regulating dynamic equilibrium between bone formation and bone resorption. Osteoblasts and osteoclasts act as sensitive cells for mechanical stimulation. Bone can transform the mechanical load generated by exercise into biological stimulation that acts on the differentiation and function of related bone cells, thereby regulating bone metabolism. In vitro experiments have indicated that different forms of mechanical stress stimulations can change the methylation level of genes such as OPN and GNAS1 to regulate their expression, which has a positive effect on bone formation. Bone tissue is a mechanically sensitive tissue, and DNA methylation can regulate bone metabolism by regulating a variety of factors.