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

15 Scopus citations


This study examined the interrelationship between transforming growth factor-beta1 (TGF-β1) and 17β-estradiol (E2) in the regulation of growth plate chondrocytes. To determine whether TGF-β1 modulates chondrocyte response to E2, 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 E2 for 24 h. The effect of TGF-β1 and E2 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 E2 affected this parameter only in RC cells, causing a dose-dependent decrease. At the highest concentration of TGF-β1 and E2, [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 E2 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 E2, 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 E2. 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. E2 affected only female cells. TGF-β1 potentiated the effect of E2 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 E2 can be modulated by local regulatory agents such as TGF- β1.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
Issue number3
StatePublished - 1999
Externally publishedYes


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


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