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

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Abstract

This study examined the interrelationship between transforming growth factor-betal (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 24h. 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. E2′ 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 10−9 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.

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Authors and Affiliations

  1. Department of Periodontology, Hebrew University Jerusalem, San Antonio, Israel, TX

    Erez Nasatzky, Dana Grinfeld & Zvi Schwartz

  2. Anatomy and Embryology, Hebrew University Jerusalem, San Antonio, TX, Israel

    Asher Ornoy

  3. Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, TX

    Barbara D. Boyan

  4. Department of Periodontology, The University of Texas Health Science Center at San Antonio, San Antonio, TX

    Barbara D. Boyan & Zvi Schwartz

  5. Department of Orthopaedics (Mail Code 7774), The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX

    Barbara D. Boyan, David D. Dean & Zvi Schwartz

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  1. Erez Nasatzky
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  2. Dana Grinfeld
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  3. Barbara D. Boyan
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Correspondence to Barbara D. Boyan.

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Nasatzky, E., Grinfeld, D., Boyan, B.D. et al. Transforming growth factor-β1 modulates chondrocyte responsiveness to 17β-estradiol. Endocr 11, 241–249 (1999). https://doi.org/10.1385/ENDO:11:3:241

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  • DOI: https://doi.org/10.1385/ENDO:11:3:241

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