Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2020 Sep 25;21(19):7080. doi: 10.3390/ijms21197080.
Age related changes to the skeleton, such as osteoporosis, increase the risk of fracture and morbidity in the elderly population. In osteoporosis, bone remodeling becomes unbalanced with an increase in bone resorption and a decrease in bone formation. Osteoclasts are large multinucleated cells that secrete acid and proteases to degrade and resorb bone. Understanding the molecular mechanisms that regulate osteoclast differentiation and activity will provide insight as to how hyper-active osteoclasts lead to pathological bone loss, contributing to diseases such as osteoporosis. Reversible modifications to the DNA such as histone acetylation, methylation, phosphorylation and ubiquitylation alters the access of transcriptional machinery to DNA and regulates gene expression and osteoclast differentiation and activity. It is critical for the management of bone related diseases to understand the role of these chromatin modifying proteins during osteoclast differentiation, as potential therapies targeting these proteins are currently under development.
骨骼的年龄相关性变化，如骨质疏松症，会增加老年人群骨折和发病的风险。在骨质疏松症中，骨重建变得不平衡，骨吸收增加，骨形成减少。破骨细胞是大型多核细胞，可分泌酸和蛋白酶降解和吸收骨。了解调节破骨细胞分化和活性的分子机制将深入了解过度活跃的破骨细胞如何导致病理性骨质流失，从而导致骨质疏松症等疾病。DNA 的可逆修饰，如组蛋白乙酰化、甲基化、磷酸化和泛素化，改变转录机制与 DNA 的接触，调节基因表达和破骨细胞分化和活性。了解这些染色质修饰蛋白在破骨细胞分化过程中的作用对于骨骼相关疾病的治疗至关重要，因为目前正在开发针对这些蛋白的潜在治疗方法。
