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Action of Estradiol on Epiphyseal Growth Plate Chondrocytes

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Abstract

Estrogen plays an important role in the human growth plate by accelerating growth and promoting epiphyseal fusion in both sexes. Nevertheless, the precise mechanisms responsible for these effects are poorly understood. In the present study, we examined the role of 17β-estradiol (E2) on cell proliferation and viability, type X collagen synthesis, alkaline phosphatase activity, and matrix calcification in primary cultures of resting, proliferating, and prehypertrophic chondrocytes derived from explants of the bovine fetal epiphyseal growth plate. Growth plate chondrocytes were isolated and separated into maturationally distinct subpopulations, which were cultured for 7–21 days to high density in either (1) serum-free medium, (2) 1 nM thyroid hormone (T3), (3) E2 concentrations ranging from 10−13 M to 10−7 M, or (4) a combination of T3 and E2. To compare E2 effects in both sexes, chondrocytes were harvested from 8 fetuses of both sexes. After hormone treatment, cell cultures were analyzed for cell number and viability, collagen type X, alkaline phosphatase (ALP), and matrix calcification. Neither DNA content nor cell viability were affected by the duration or type of hormone treatment. By itself, E2 stimulated maturation of all subpopulations only in pharmacologic doses (10−7 M). Physiologic E2 concentrations were no different than negative controls treated with ITS (insulin, transferrin, and selenite). Regardless of E2 concentrations, the addition of E2 to 1 nM T3 did not appreciably affect the response to T3 alone, which stimulates maturation of the phenotype. All effects were comparable in both male and female chondrocytes, in all cell subpopulations (maturation stages) and fetuses of varying gestational age. These findings indicate that at physiologic concentrations, the effects of E2 on fetal bovine growth plate chondrocyte appear to be indirect and independent of T3, suggesting that, in vivo, E2 acts in concert with other factors or hormones to induce fusion of the growth plate.

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Acknowledgments

The Canadian Institutes of Health Research generously funded this study.

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Authors and Affiliations

  1. Montreal Children’s Hospital, McGill University Health Centre, 2300 Tupper St., Montreal, Quebec, H3H IP3, Canada

    C. Rodd

  2. Orthopaedic Research Laboratory, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada

    N. Jourdain & M. Alini

  3. AO Research Institute, Davos, Switzerland

    M. Alini

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  1. C. Rodd
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  2. N. Jourdain
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  3. M. Alini
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Correspondence to C. Rodd.

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Rodd, C., Jourdain, N. & Alini, M. Action of Estradiol on Epiphyseal Growth Plate Chondrocytes. Calcif Tissue Int 75, 214–224 (2004). https://doi.org/10.1007/s00223-004-0197-7

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  • DOI: https://doi.org/10.1007/s00223-004-0197-7

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