Effects of testosterone and 17β-estradiol on osteogenic and adipogenic differentiation capacity of human bone-derived mesenchymal stromal cells of postmenopausal women

TY - JOUR

T1 - Effects of testosterone and 17β-estradiol on osteogenic and adipogenic differentiation capacity of human bone-derived mesenchymal stromal cells of postmenopausal women

AU - Glenske, Kristina

AU - Schuler, Gerhard

AU - Arnhold, Stefan

AU - Elashry, Mohamed I

AU - Wagner, Alena-Svenja

AU - Barbeck, Mike

AU - Neumann, Elena

AU - Müller-Ladner, Ulf

AU - Schnettler, Reinhard

AU - Wenisch, Sabine

N1 - © 2019 The Author(s).

PY - 2019/12

Y1 - 2019/12

N2 - 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 PPARγ and AR expression, independent of anastrozole. Regardless of the culture conditions, ERα was detectable whilst ERβ was not. In conclusion, aromatase activity is limited to differentiated hMSCs and the resulting 17β-estradiol enhances late osteogenic differentiation stages via ERα. Adipogenic differentiation, on the other hand, is reduced by both sex steroids: testosterone via AR and 17β-estradiol.

AB - 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 PPARγ and AR expression, independent of anastrozole. Regardless of the culture conditions, ERα was detectable whilst ERβ was not. In conclusion, aromatase activity is limited to differentiated hMSCs and the resulting 17β-estradiol enhances late osteogenic differentiation stages via ERα. Adipogenic differentiation, on the other hand, is reduced by both sex steroids: testosterone via AR and 17β-estradiol.

U2 - 10.1016/j.bonr.2019.100226

DO - 10.1016/j.bonr.2019.100226

M3 - SCORING: Journal article

C2 - 31709277

VL - 11

SP - 100226

JO - BONE REP

JF - BONE REP

SN - 2352-1872

ER -