Effects of Testosterone and 17β-estradiol on Osteogenic and Adipogenic Differentiation Capacity of Human Bone-derived Mesenchymal Stromal Cells of Postmenopausal Women

Progressive bone loss is a predominant symptom of aging and osteoporosis. Therefore, the effects of sex steroids (i.e. testosterone and 17β-estradiol) on the differentiation capacity of human bone-derived mesenchymal stromal cells (hMSCs), as progenitors of osteoblasts and adipocytes, are of particular interest. The objectives of the present study were, thus, to elucidate whether bone-derived hMSCs of postmenopausal women produce aromatase (CYP19A1) and, whether they modulate their differentiation behaviour in response to testosterone and 17β-estradiol (E2), in relation to their steroid receptor expression. Supplementation of testosterone resulted in a considerable formation of E2 under osteogenic and adipogenic culture conditions, whereas E2 synthesis remained minimal in the cells cultured in basal medium. Concomitant with high aromatase expression and 17β-estradiol formation of the cells cultured in osteogenic medium supplemented with testosterone, a distinct promotion of late-stage osteogenesis was found, as shown by significant matrix mineralization and a notable increase in osteogenic markers. These effects were abrogated by the aromatase inhibitor anastrozole. Under adipogenic conditions, testosterone reduced the occurrence of lipid droplets and led to a decrease in and expression, independent of anastrozole. Regardless of the culture conditions, was detectable whilst was not. In conclusion, aromatase activity is limited to differentiated hMSCs and the resulting 17β-estradiol enhances late osteogenic differentiation stages via . Adipogenic differentiation, on the other hand, is reduced by both sex steroids: testosterone via and 17β-estradiol.