Osteoclasts and Transforming Growth Factor-β: Estrogen-Mediated Isoform-Specific Regulation of Production

J. A. Robinson, B. L. Riggs, T. C. Spelsberg, Merry Jo Oursler

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Abstract

Estrogen deficiency induced by menopause leads to an increase in bone resorption that is not compensated for by a comparable increase in bone formation, resulting in excessive bone loss. Clinically, estrogen replacement reverses these processes, but the mechanisms by which this takes place are not completely understood. Both osteoclasts and osteoblasts contain functional estrogen receptors and, therefore, may be directly involved in these responses. Because both osteoclasts and osteoblasts secrete transforming growth factor-β (TGFβ), and because 17β-estradiol (E2) treatment increases TGFβ production by osteoblast-like cells in vitro, we have investigated the possibility that E2 also may increase the production of TGFβ by isolated osteoclasts in vitro. Highly purified avian osteoclasts were treated with either vehicle or E2, and TGFβ protein accumulation in culture was measured by bioassay. Although an E2 dose-dependent increase in TGFβ protein accumulation in osteoclast-conditioned medium was measured at 4 h of treatment, a steroid dose-dependent decrease in the accumulation of active TGFβ was measured after 18 h of estrogen treatment. The steroid specificity of the increased TGFβ accumulation was confirmed by demonstrating that the E2-induced increase in TGFβ protein levels in the medium was inhibited by cotreatment with a specific E2 antagonist. Interestingly, E2 treatment induced a TGFβ isoform change from TGFβ2 to predominantly TGFβ3. Thus, the data suggest that a direct action of E2 on osteoclasts to lower resorption activity may be mediated by autocrine/paracrine production and activation of TGFβ, perhaps including modulation of specific isoform production.

Original languageEnglish (US)
Pages (from-to)615-621
Number of pages7
JournalEndocrinology
Volume137
Issue number2
StatePublished - 1996

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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