Differential responsiveness to 17β-estradiol of mesenchymal stem cells from postmenopausal women between osteoporosis and osteoarthritis

Abstract

Differential osteogenic potential and responsiveness to 17β-estradiol (E2) of mesenchymal stem cells (MSCs) were found between postmenopausal women with osteoporosis (OP) and osteoarthritis (OA). These results suggest differential biological mechanisms of estrogen deficiency in regulation of bone remodeling between OP and OA. OP and OA are two common disorders in postmenopausal women. The inverse relationship has been suggested between OP and OA, but their mechanisms that relate to estrogen deficiency are not fully understood. The aim of this study was to compare the differential responsiveness to E2 of MSCs from osteoporotic versus osteoarthritic donors. Twenty postmenopausal patients, ten with osteoporotic hip fractures and ten with hip osteoarthritis, were included into this study. MSCs were derived from cancellous bones of femoral heads from OA and OP donors and cultured in osteogenic and adipogenic medium with or without E2 added. The alkaline phosphatase (ALP) activity, calcium content, calcified nodules, lipid droplets, messenger RNA (mRNA) expression of ALP, osteocalcin (OC), collagen 1α (COL1α), peroxisome proliferators-activated receptor γ2 (PPARγ2) and lipoprotein lipase (LPL) were measured and compared between two groups with OP and OA. In osteogenic medium, ALP activity, calcium content and mRNA expression of OC and COL1α in MSCs from OA were significantly higher than those from OP group. In adipogenic condition, there was no significant difference in lipid droplets formation and mRNA expression of PPARγ2 and LPL between OP and OA groups. With E2 added in osteogenic medium, ALP activity, calcium content and OC mRNA were significantly higher in OP group than in OA group, whereas E2 had no significant effect on lipid droplet formation and mRNA expression of PPARγ2 and LPL. Differential osteogenic potential and responsiveness to E2 of MSCs were found between postmenopausal women with OP and OA. These results may provide information for clinical application of MSCs in the differential setting of estrogen deficiency.