Role of RANK ligand in mediating increased bone resorption in early postmenopausal women
Role of RANK ligand in mediating increased bone resorption in early postmenopausal women
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DOI：
10.1172/jci200317215
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发表时间：
2003-04-01
影响因子：
15.9
通讯作者：
Riggs, BL
中科院分区：
文献类型：
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作者：
Eghbali-Fatourechi, G;Khosla, S;Riggs, BL
在啮齿类动物中的研究表明，雌激素缺乏期间，各种细胞因子作为破骨细胞生成增加的旁分泌介质，但破骨细胞生成的最终效应因子RANKL的增加尚未得到证实。因此，我们使用FITC结合的骨保护素-Fc（OPG-Fc-FITC）作为探针，通过双色流式细胞术分离表面表达RANKL的骨髓单核细胞。分别在12名绝经前妇女（A组）、12名绝经早期妇女（B组）和12名年龄匹配的雌激素治疗的绝经后妇女（C组）中，通过使用抗骨碱性磷酸酶（BAP）、CD 3和CD 20的Ab，将细胞表征为前成骨骨髓基质细胞（MSC）、T淋巴细胞或B淋巴细胞。对于MSC、T细胞、B细胞和总RANKL表达细胞，与A组和C组相比，B组中OPG-Fc-FITC的荧光强度（每个细胞RANKL表面浓度的指数）增加了2 - 3倍。此外，在合并组中，每个细胞的RANKL表达与所有三种细胞类型中的骨吸收标志物、血清I型胶原C-末端肽和尿I型胶原N-末端肽直接相关，与总RANKL表达细胞的血清17 β-雌二醇呈负相关。这些数据表明，骨髓细胞上RANKL的上调是雌激素缺乏诱导的骨吸收增加的重要决定因素。
Studies in rodents have implicated various cytokines as paracrine mediators of increased osteoclastogenesis during estrogen deficiency, but increases in RANKL, the final effector of osteoclastogenesis, have not been demonstrated. Thus, we isolated bone marrow mononuclear cells expressing RANKL on their surfaces by two-color flow cytometry using FITC-conjugated osteoprotegerin-Fc (OPG-Fc-FITC) as a probe. The cells were characterized as preosteoblastic marrow stromal cells (MSCs), T lymphocytes, or B lymphocytes by using Ab's against bone alkaline phosphatase (BAP), CD3, and CD20, respectively, in 12 premenopausal women (Group A), 12 early postmenopausal women (Group B), and 12 age-matched, estrogen-treated postmenopausal women (Group C). Fluorescence intensity of OPG-Fc-FITC, an index of the surface concentration of RANKL per cell, was increased in Group B over Groups A and C by two- to threefold for MSCs, T cells, B cells, and total RANKL-expressing cells. Moreover, in the merged groups, RANKL expression per cell correlated directly with the bone resorption markers, serum C-terminal telopeptide of type I collagen and urine N-telopeptide of type I collagen, in all three cell types and inversely with serum 17beta-estradiol for total RANKL-expressing cells. The data suggest that upregulation of RANKL on bone marrow cells is an important determinant of increased bone resorption induced by estrogen deficiency.