Estrogen specifically stimulates expression and production of osteoprotegerin from rheumatoid synovial fibroblasts.
Estrogen specifically stimulates expression and production of osteoprotegerin from rheumatoid synovial fibroblasts.
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DOI：
10.3892/ijmm.15.5.827
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发表时间：
2005-05
影响因子：
5.4
通讯作者：
M. Mitani;Y. Miura;R. Saura;A. Kitagawa;T. Fukuyama;A. Hashiramoto;S. Shiozawa;M. Kurosaka;S. Yoshiya
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文献类型：
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作者：
M. Mitani;Y. Miura;R. Saura;A. Kitagawa;T. Fukuyama;A. Hashiramoto;S. Shiozawa;M. Kurosaka;S. Yoshiya
我们研究了雌激素对类风湿关节炎（RA-FLS）中人成纤维细胞样滑膜细胞的影响，重点是NF-κ B配体受体激活因子（RANKL）及其诱饵受体骨保护素（OPG），破骨细胞的形成和功能调节因子在RA骨侵蚀中起重要作用。雌激素影响骨质疏松症和临床RA的发病。RA-FLS对雌激素的细胞反应通过两种高亲和力的雌激素受体（ER）启动。在10（-6）M 17 β-雌二醇（E2）存在下培养RA-FLS可增加雌激素受体（ER）-α的表达，但不增加ER-β的表达。OPG mRNA表达显著增加，而RANKL mRNA未受影响。E2处理还显著增加了培养上清液中OPG的释放量。纯雌激素拮抗剂ICI 182780特异性拮抗OPG和ER-α的增加。选择性ER调节剂他莫昔芬不增加OPG。结果表明，雌激素通过作用于ER-α刺激RA-FLS分泌OPG，这可能防止RA的骨侵蚀。
We studied the effects of estrogen on human fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) focusing on receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), the osteoclast formation and function regulators that have a substantial role in bone erosion of RA. Estrogen influences osteoporosis and the onset of RA clinically. The cellular responses of RA-FLS to estrogen are initiated via two high-affinity estrogen receptors (ERs). Culture of RA-FLS in the presence of 10(-6) M 17beta-estradiol (E2) increased expression of estrogen receptor (ER)-alpha, but not ER-beta. OPG mRNA expression was significantly increased, whereas RANKL mRNA was unaffected. E2 treatment also significantly increased the amount of OPG released in the culture supernatant. The increase of OPG and ER-alpha was specifically antagonized by the pure estrogen antagonist ICI 182780. Tamoxifen, a selective ER moderator, did not increase OPG. The results indicate that estrogen stimulates secretion of OPG from RA-FLS by acting on ER-alpha, which likely prevents bone erosion in RA.