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Role of RANK ligand in mediating increased bone resorption in early postmenopausal women
Guitty Eghbali-Fatourechi, … , David L. Lacey, B. Lawrence Riggs
Guitty Eghbali-Fatourechi, … , David L. Lacey, B. Lawrence Riggs
Published April 15, 2003
Citation Information: J Clin Invest. 2003;111(8):1221-1230. https://doi.org/10.1172/JCI17215.
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Role of RANK ligand in mediating increased bone resorption in early postmenopausal women

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Abstract

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 17β-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.

Authors

Guitty Eghbali-Fatourechi, Sundeep Khosla, Arunik Sanyal, William J. Boyle, David L. Lacey, B. Lawrence Riggs

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Figure 4

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Changes in OPG-Fc-FITC fluorescence as an index of mean RANKL surface co...
Changes in OPG-Fc-FITC fluorescence as an index of mean RANKL surface concentration per cell (mean ± SEM). The premenopausal women (Group A) are shown by the white bars, the untreated postmenopausal women (Group B) by gray bars, and the estrogen-treated postmenopausal women (Group C) by black bars. There is a highly significant (ANOVA P values as indicated) difference among three groups. There is a two- to threefold significant increase of the mean RANKL fluorescence intensity per cell in Group B over Group A (*) and a somewhat smaller significant increase in Group B over Group C (**) as analyzed by the Student-Newman-Keuls test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 6 patents
Referenced in 1 clinical guideline sources
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