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

We previously reported a non-enzymatic method for isolation of human bone c ells in culture that display osteoblastic features and respond to 1,25 dihy droxy vitamin D (1,25) and to parathyroid hormone (PTH). The present study was undertaken to analyze the response of cultured human bone cells to 17 b eta -estradiol (E2) and to dihydrotestosterone (DHT) as a function of gende r and age. Cultured human bone cells, obtained from biopsies during orthope dic surgery, were divided into four groups defined by gender and age: pre- and post-menopausal healthy non-osteoporotic women that were not under horm one replacement therapy (HRT) and mature (< 55-year-old) and older (> 60-ye ar-old) men. We found gender specific responses to gonadal steroids using t he specific activity of the brain type (BB) isozyme of creatine kinase (CK) as a response marker. Constitutive levels of CK activity did not change wi th age or gender and the enzyme extracted from cells from the different sex es 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 mann er, i.e. CK from female derived cells responded to E2 only and the enzyme f rom male derived cells responded to DHT only. In female derived cells the r esponse 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 eithe r decreased proportion of mature osteoblasts and/or their differentiation s tate and/or changes in the levels of estrogen receptor(s), coactivators or corepressors in these cells. These results extend our knowledge of human os teoblast biology (beyond murine cells) and are therefore more relevant for developing models for treatment of human metabolic bone diseases such as po st-menopausal osteoporosis.