Transforming growth factor-β1 modulates chondrocyte responsiveness to 17β-estradiol

Erez Nasatzky, Dana Grinfeld, Barbara D. Boyan, David D. Dean, Asher Ornoy, Zvi Schwartz

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

This study examined the interrelationship between transforming growth factor-beta1 (TGF-β1) and 17β-estradiol (E 2) in the regulation of growth plate chondrocytes. To determine whether TGF-β1 modulates chondrocyte response to E 2, we used cells isolated from the resting zone (RC) and growth zone (GC) of costochondral cartilage. Confluent, fourth-passage cultures were pretreated with rhTGF-β1 for 24 h, followed by treatment with E 2 for 24 h. The effect of TGF-β1 and E 2 alone, or the sequential combination, were examined by measuring [ 3H]-thymidine incorporation (proliferation), alkaline phosphatase (AP) specific activity (differentiation), and [ 35S]-sulfate incorporation (matrix synthesis). TGF-β1 alone increased [ 3H]-thymidine incorporation in both female and male RC and GC cells, but E 2 affected this parameter only in RC cells, causing a dose-dependent decrease. At the highest concentration of TGF-β1 and E 2, [ 3H]-thymidine incorporation in female GC cells was the same as seen in untreated control cultures. In male GC cells, [ 3H]-thymidine incorporation in cultures treated with TGF-β1 and E 2 exhibited a comparable increase, as was seen in cultures treated with TGF-β1 alone. TGF-β1 caused a biphasic stimulation in AP that was maximal at 0.22 ng/mL, in both female and male RC and GC cells. Eβ, however, affected only female cells. Whereas the effect of TGF-β1 predominated in RC and GC male cells, the biphasic stimulation caused by E 2, maximal at 109 M, predominated in female RC cells. In female GC cells, however, TGF-β1 caused a synergistic response, resulting in enhanced AP specific activity in cultures pretreated with 0.22 ng/mL of TGF-β1 and 10 -8 M E 2. TGF-β1 alone caused dose- dependent increases in [ 35S]sulfate incorporation in female RC and GC cells, as well as in male GC cells, but had no effect on male RC cells. E 2 affected only female cells. TGF-β1 potentiated the effect of E 2 on this parameter, resulting in synergistic increases in the female cells. This is the first demonstration of a gender-specific response to TGF-β1 in chondrocytes. These results suggest that chondrocyte response to a systemic hormone such as E 2 can be modulated by local regulatory agents such as TGF- β1.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalEndocrine
Volume11
Issue number3
StatePublished - Dec 1 1999

Keywords

  • 17β-estradiol
  • Chondrocyte
  • Growth plate
  • TGF-β

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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