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Age and gender specific stimulation of creatine kinase specific activity by gonadal steroids in human bone-derived cells in culture

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Abstract

We previously reported a non-enzymatic method for isolation of human bone cells in culture that display osteoblastic features and respond to 1,25 dihydroxy vitamin D (1,25) and to parathyroid hormone (PTH). The present study was undertaken to analyze the response of cultured human bone cells to 17gB-estradiol (E2) and to dihydrotestosterone (DHT) as a function of gender and age. Cultured human bone cells, obtained from biopsies during orthopedic surgery, were divided into four groups defined by gender and age: pre- and post-menopausal healthy non-osteoporotic women that were not under hormone replacement therapy (HRT) and mature (<55-year-old) and older (>60-year-old) men. We found gender specific responses to gonadal steroids using the specific activity of the brain type (BB) isozyme of creatine kinase (CK) as a response marker. Constitutive levels of CK activity did not change with age or gender and the enzyme extracted from cells from the different sexes and ages did not respond to either progesterone (P) or to 1,25. CK from the different cells responded to gonadal steroids in a gender specific manner, i.e. CK from female derived cells responded to E2 only and the enzyme from male derived cells responded to DHT only. In female derived cells the response to E2 declined significantly with age, while the response to DHT in CK from male derived cells did not vary with age. This may be due to either decreased proportion of mature osteoblasts and/or their differentiation state and/or changes in the levels of estrogen receptor(s), coactivators or corepressors in these cells. These results extend our knowledge of human osteoblast biology (beyond murine cells) and are therefore more relevant for developing models for treatment of human metabolic bone diseases such as post-menopausal osteoporosis.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    S. Katzburg & A. Ornoy

  2. Department of Orthopaedics, Shaarei Zedek Hospital, Jerusalem, Israel

    D. Hendel

  3. CNRS, UPR 1524, Paris, France

    M. Lieberherr

  4. Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel

    A. M. Kaye

  5. Tel-Aviv Sourasky Medical Center, Institute of Endocrinology, 6, Weizmann St., Tel-Aviv, 64239, Israel

    D. Somjen

Authors
  1. S. Katzburg
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  2. A. Ornoy
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  3. D. Hendel
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  4. M. Lieberherr
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  5. A. M. Kaye
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  6. D. Somjen
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Correspondence to D. Somjen.

Additional information

In partial fulfillment of the requirements for a Ph.D. Thesis of the Hadassah Medical School, Hebrew University, Jerusalem.

This project was supported in part by private donation to D. Somjen in memory of the late Haim Ben-Yitzhaq

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Katzburg, S., Ornoy, A., Hendel, D. et al. Age and gender specific stimulation of creatine kinase specific activity by gonadal steroids in human bone-derived cells in culture. J Endocrinol Invest 24, 166–172 (2001). https://doi.org/10.1007/BF03343837

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