Role of RANK ligand in mediating increased bone resorption in early postmenopausal women

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1221-1230
Number of pages10
JournalJournal of Clinical Investigation
Volume111
Issue number8
DOIs
StatePublished - Apr 2003

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RANK Ligand
Bone Resorption
Fluorescein-5-isothiocyanate
Estrogens
Stromal Cells
Osteogenesis
Bone Marrow Cells
B-Lymphocytes
Bone Marrow
T-Lymphocytes
Osteoprotegerin
Collagen Type I
Alkaline Phosphatase
Estradiol
Rodentia
Flow Cytometry
Up-Regulation
Color
Biomarkers
Fluorescence

ASJC Scopus subject areas

  • Medicine(all)

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Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. / Eghbali-Fatourechi, Guitty; Khosla, Sundeep; Sanyal, Arunik; Boyle, William J.; Lacey, David L.; Riggs, B. Lawrence.

In: Journal of Clinical Investigation, Vol. 111, No. 8, 04.2003, p. 1221-1230.

Research output: Contribution to journalArticle

Eghbali-Fatourechi, Guitty ; Khosla, Sundeep ; Sanyal, Arunik ; Boyle, William J. ; Lacey, David L. ; Riggs, B. Lawrence. / Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 8. pp. 1221-1230.
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