title: Methylation of the promoter A of estrogen receptor alpha gene in hBMSC and osteoblasts and its correlation with homocysteine.
abstract: Recent studies have shown that adult osteoporosis could be induced by ageing and estrogen deficiency and homocysteine (Hcy) is an independent risk factor of fracture in osteoporosis patients. In this study, we found hypermethylation of the promoter A region in the estrogen receptor alpha (ERα) gene, and methylation in 70.59% of 68 post-menopausal women, whose methylation degree was significantly higher than the pre-menopausal women (P < 0.05). Their methylation frequency was detected only 26.67% in 30 subjects. An obvious correlation between the degree of methylation in ERα gene and the level of Hcy (r = 0.809, P < 0.05) was explored. The cultured human bone marrow strom cells (hBMSC) and osteoblasts treated by Hcy resulted in de novo methylation of the promoter A region in the ERα gene and suppressed proliferation and differentiation with time and dose dependence. Meanwhile, ERα gene mRNA in osteoblast-like cells treated by Hcy was much lower than the control group (P < 0.05). Thus, both in vivo and in vitro data showed that Hcy could promote hypermethylation of the promoter A region and reduce ERα mRNA transcription, which may be an important mechanism for the pathogenesis of postmenopausal osteoporosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Lv
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Ma
authors.forename: Tuanjie
authors.initials: T
authors.lastname: Che
authors.forename: Yirong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015519:Bone Density / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006710:Homocysteine / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism*; D010024:Osteoporosis / Q000378:metabolism; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D006710:Homocysteine