Modulation of transforming growth factor-β production in normal human osteoblast-like cells by 17β-estradiol and parathyroid hormone

Merry Jo Oursler, Case Cortese, Philip Keeting, Marlys A. Anderson, Susan K. Bonde, B. Lawrence Riggs, Thomas C. Spelsberg

Research output: Contribution to journalArticlepeer-review

244 Scopus citations


Although our laboratory has reported that normal human osteoblast-like (hOB) cells contain estrogen receptors, we have failed to find major effects of 17β-estradiol (E2) on modulation of proliferation of bone matrix protein production by hOB cells. Because the major effect of E2 in vivo is to decrease bone resorption and because transforming growth factor-β (TGF-β) has been reported to decrease osteoclast-mediated bone resorption, we have tested the hypothesis that the effect of E2 on osteoclast activity is, at least in part, indirectly mediated by enhancing production of TGF-β by osteoblasts. We therefore have extended our studies to examine possible TGF-β gene expression including the modulation of the release of TGF-β by E2 in near homogenous populations of hOB cells. TGF-β protein production was measured using growth inhibition of CCL-64 cells and verified by blocking effects with anti-TGF-β antibodies. TGF-β, messenger RNA (mRNA) steady state levels were assessed by northern blot analysis and quantitated by densitometric measurement using 18S ribosomal RNA as a reference. There was an E2 dose-dependent increase in TGF-β protein production within 24 h of challenge with E2. Northern blots from these cells demonstrated a dose-dependent increase in steady state mRNA levels of TGF-β1 within 6 h of treatment. PTH was also a potent stimulator of TGF-β protein and message levels in a dose-dependent manner. Interestingly, coincubation of equimolar concentrations of E2 and PTH (10-8 M) abrogated the stimulation of TGF-β, mRNA and protein. Decreasing the relative concentration of PTH in this coincubation with E2 increased TGF-β1 mRNA and protein levels. These data support the fact that E2 modulates TGF-β production in osteoblasts. In this manner TGF-β may mediate E2 inhibition of osteoclast activity.

Original languageEnglish (US)
Pages (from-to)3313-3320
Number of pages8
Issue number6
StatePublished - Dec 1991

ASJC Scopus subject areas

  • Endocrinology


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