雌激素受体α基因甲基化与骨质疏松关系的研究进展

摘要

妇女绝经后体内雌激素水平显著下降,发生骨质疏松和骨折的风险显著增加.DNA甲基化作为表观遗传作用机制之一,与骨质疏松的发生有着重要关系.雌激素受体α基因甲基化水平升高会抑制雌激素受体α基因的表达,进而影响骨的新陈代谢,但具体作用机制有待于进一步研究.这种甲基化的状态是可以逆转的,通过干预基因甲基化,可以影响骨形成和骨重吸收的过程,进而为诊断和治疗骨质疏松提供新的思路.研究显示血清同型半胱氨酸(Hcy)会影响雌激素受体α基因甲基化水平,绝经后妇女平均血清Hcy浓度显著高于绝经前妇女,提示血清Hcy浓度可以作为早期筛查骨质疏松的指标之一;葛根素达到合适浓度后可抑制成骨细胞雌激素受体α基因甲基化,增强细胞ERαmRNA表达,进而促使成骨细胞增殖分化,从而用于骨质疏松的治疗.通过分析阐明雌激素受体α基因甲基化与骨质疏松的关系,可以早期筛选骨质疏松的高危人群,更简便快捷地诊断骨质疏松,为临床进行基因诊断提供理论依据;可以选择性地开发调节雌激素受体α基因甲基化药物,从而使治疗骨质疏松的靶向性更强,为骨质疏松的基因治疗提供理论依据.%Reduced bioavailability of estrogen increases osteoporosis and fracture risk significantly in postmenopausal women.As one of the mechanism of epigenetie mechanism,DNA methylation has an important relationship with the occurrence of osteoporosis.The increase of estrogen receptor alpha gene methylation inhibits the expression of estrogen receptor alpha gene,and then affects bone metabolism,but the specific mechanism needs further study.This methylation status can be reversed,and the process of bone formation and bone resorption can be influenced by the intervention of gene methylation,which provides a new way for the diagnosis and treatment of osteoporosis.Studies have shown that the level of serum homocysteine (Hcy) affects the status of estrogen receptor alpha gene methylation.On average,the serum Hcy concentration in postmenopausal women is significantly higher than that in premenopausal women,indicating that serum Hcy concentration can be used as one of the indicators of early osteoporosis screening.Puerarin inhibits the estrogen receptor alpha gene methylation,and enhances the expression of ER alpha mRNA,and then promotes the proliferation and differentiation of osteoblasts,which can be used for the treatment of osteoporosis.Through the analysis of the relationship between estrogen receptor alpha gene methylation and osteoporosis,we can screen osteoporosis high-risk groups early,and provide theoretical basis for more simple and rapid diagnosis of osteoporosis.We can also selectively develop drugs regulating estrogen receptor alpha gene methylation,making the treatment of osteoporosis more targeted,and provide a theoretical basis for the gene therapy of osteoporosis.