Estrogen treatment decreases the osteoclast precursor population and TNF receptor expression by these cells in vivo in postmenopausal women

J. A. Clowes, A. H. Undale, Salman Kirmani, G. Z. Eghbali-Fatourechi, L. K. McCready, M. J. Oursler, S. Khosla, L. R. Riggs

Research output: Contribution to journalArticle


Previous animal and in vitro studies have established the CD14+ monocyte as the cellular precursor which differentiates into mature osteoclasts. Monocytes express key surface receptors, including c-Fms (the receptor for M-CSF), RANK (the receptor for RANKL), and TNFR1 and TNFR2 (the receptors for TNFα), which are involved in the differentiation of these cells into osteoclasts, at which point the cells also express the calcitonin receptor (CTR). Furthermore, the recently discovered OSCAR and TREM2 receptors provide important co-stimulatory functions for osteoclast development. However, the impact of estrogen (E) on monocyte differentiation and function into osteoclast precursors in vivo in humans has not yet been determined. Thus, we examined effects of E on the expression of these surface receptors on bone marrow mononuclear cells (MNCs) following 4 weeks of E treatment (100 üg/d estradiol patches; n = 17) vs. untreated (control; n = 17) postmenopausal women. The Mean Fluorescence Intensity (MFI, a surrogate for the concentration/cell of the protein) for each receptor as well as the percentage of cells (as a fraction of bone marrow MNCs) expressing the various receptors was assessed using flow cytometry. As shown in the Table, E treatment resulted in a significant decrease in the MFI for TNFR2 on bone marrow MNCs. Moreover, the percentage of bone marrow MNCs co-expressing RANK/CD14, TNFR2/CTR, or CTR was also significantly reduced by E. By contrast, E had no effect on expression of c-Fms, OSCAR, or TREM2. Table.These studies thus represent the first systematic examination of the effects of E on osteoclast precursor populations in vivo in humans. Collectively, they indicate that E decreases the differentiation of monocytes towards mature osteoclasts and suggests this is mediated principally through regulation of the TNF receptor family rather then through modulating co-stimulatory receptor expression.

Original languageUndefined/Unknown
JournalDepartment of Paediatrics and Child Health
Publication statusPublished - 1 Sept 2006

Cite this