OBJECTIVE: To determine whether estrogen regulates mesenchymal stem cell (MSC) activity in bone marrow from osteoporotic postmenopausal women. METHODS: MSCs were collected from bone marrows which were aspirated simultaneously during iliac bone graft procedures in spine fusion surgery in osteoporotic postmenopausal women. We investigated proliferation, differentiation, osteogenic activity, and estrogen receptor (ER) α and β mRNA expression of primary culture MSCs isolated from four osteoporotic postmenopausal women, treated in vitro with or without 17β-estradiol. The expression of alkaline phosphatase (ALP), osteocalcin, interleukin-6, ERα and ERβ mRNA was evaluated. RESULTS: The expression of ALP and osteocalcin mRNA was detected during the cultures of MSCs and was observed to increase up to day 20. As compared with MSCs not treated with estradiol, a significant increase in DNA content, ERα mRNA, and ALP mRNA expression was observed in cultures with estradiol. The mRNA expression of osteocalcin and interleukin-6 was significantly lower in MSCs treated with estradiol than those without estradiol. There was no significant difference in the mRNA expression of ERβ between MSCs cultured with and without estradiol. CONCLUSIONS: In the proper environment, MSCs from osteoporotic women can differentiate into osteoblasts and estrogen enhances the osteogenic activity possibly via ERα activity.