The effects of 17-estradiol on cellular proliferation and calcification of human mesenchymal stem cell during osteogenesis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-217
Jenny Zhengyi Wang*1, Joshua Lewis2, Lawrence Liew2, Anthony C Buzzai3, Jeremy Tan4, Gerard Hardisty4, Jeffery Hamdrof5, Minghao Zheng6 and Richard L Prince7
1University of Western Australia, Nedlands, Australia, 2University of Western Australia, 3Murdoch University, Murdoch, Australia, 4Sir Charles Gairdner Hospital, Nedlands, Australia, 5Sir Charles Gairdner Hospital, Nedlands, 6University of Western Australia, Australia, 7Sir Charles Gairdner Hosp, Nedlands, Australia

Bone structure is profoundly affected by exposure to estrogen throughout life. Multipotent human adipose-tissue derived stem cells (ADSC) and bone marrow derived stem cells (BMSC) were used as osteoblast precursor models to investigate the role of estrogen on osteoblast cellular proliferation and function during osteogenic differentiation.


Matching ADSC and BMSC from 8 female individuals were induced to osteogenic lineage by culturing in osteogenic media (OSM). 17β-estradiol (10-8M), the estrogen receptor α (ERα) blocker ICI (10-8M) and the aromatase inhibitor letrozole (10-7M) were added to OSM to identify the role of exogenous vs. endogenous estradiol in the system.


In ADSCs, endogenous estradiol production was decreased by 30% in letrozole treated cells, resulting in the significantly decreased proliferation compared to OSM (P < 0.05). The addition of 17β-estradiol to OSM did not increase cellular proliferation, however by blocking the ERα signalling pathway reduced cellular proliferation was also observed. The addition of 17β-estradiol significantly increased extracellular calcification compared to OSM (mean difference +3.71 ± 0.72%, P = 0.002), an effect reversed by blocking the ERα signalling pathway (mean difference from OSM + 17β-estradiol -4.13 ± 0.72%, P < 0.001)  or inhibiting endogenous estradiol production (mean difference +3.92 ± 0.69%, P < 0.001). This effect of blocking endogenous estradiol production was reversed with the addition of 17β-estradiol (P = 0.003).

Similar effect of estradiol was observed in BMSC model. A reduced cellular proliferation was observed in both letrozole treated and ICI treated cells at early osteogenic stage. The addition of 17β-estradiol to OSM significantly increased extracellular calcification (mean difference from OSM +6.06 ± 1.28%, P = 0.004), an effect reversed by inhibiting endogenous estradiol production (mean difference - 5.93 ± 0.95%, P < 0.001). However this effect is not reversed by blocking ERα signalling pathway (P = 0.141). Gene expression assay demonstrated that BMSC showed higher mRNA level of both ERα (P = 0.003) and ERβ (P = 0.008) compared to ADSC over osteogenic differentiation.


17β-estradiol stimulates ADSC cellular proliferation and osteogenic function mainly through the ERα pathway. Whilst similar observed effects on BMSC proliferation and osteogenic function were likely mediated by both the ERα and ERβ pathways. Results of this study identify the specific effect of 17β-estradiol on osteoblast maintenance and development separate to its effect on osteoclast function.

Nothing to Disclose: JZW, JL, LL, ACB, JT, GH, JH, MZ, RLP

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