M-CSF neutralization and Egr-1 deficiency prevent ovariectomy-induced bone loss

Simone Cenci, M. Neale Weitzmann, M. A. Gentile, M. C. Aisa, Roberto Pacifici

Research output: Contribution to journalArticle

Abstract

Increased stromal cell production of M-CSF, an event caused by enhanced phosphorylation of the nuclear protein Egr-1, is central to the mechanism by which estrogen (E2) deficiency upregulates osteoclast (OC) formation. However, the contribution of enhanced M-CSF production to the bone loss induced by E2 deficiency remains to be determined. We found that treatment with an Ab that neutralizes M-CSF in vivo completely prevents the rise in OC number, the increase in bone resorption, and the resulting bone loss induced by ovariectomy (ovx). We also found that adult, intact Egr-1-deficient mice, a strain characterized by maximally stimulated stromal cell production of M- CSF, exhibit increased bone resorption and decreased bone mass. In these mice, treatment with anti-M-CSF Ab restored normal levels of bone resorption, thus confirming that increased M-CSF production accounts for the remodeling abnormalities of Egr-1-deficient mice. Consistent with the failure of ovx to further increase M-CSF production in Egr-1-deficient mice, ovx neither increased bone resorption further, nor caused bone loss in these animals. In summary, the data demonstrate that E2 deficiency induces M-CSF production via an Egr-1-dependent mechanism that is central to the pathogenesis of ovx- induced bone loss. Thus, Egr-1 and M-CSF are critical mediators of the bone sparing effects of E2 in vivo.

Original languageEnglish
Pages (from-to)1279-1287
Number of pages9
JournalJournal of Clinical Investigation
Volume105
Issue number9
Publication statusPublished - May 2000

ASJC Scopus subject areas

  • Medicine(all)

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    Cenci, S., Weitzmann, M. N., Gentile, M. A., Aisa, M. C., & Pacifici, R. (2000). M-CSF neutralization and Egr-1 deficiency prevent ovariectomy-induced bone loss. Journal of Clinical Investigation, 105(9), 1279-1287.