The authors have no conflict of interest.
Human Osteoblasts' Proliferative Responses to Strain and 17β-Estradiol Are Mediated by the Estrogen Receptor and the Receptor for Insulin-Like Growth Factor I†
Article first published online: 1 APR 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 4, pages 593–602, April 2002
How to Cite
Cheng, M. Z., Rawlinson, S. C. F., Pitsillides, A. A., Zaman, G., Mohan, S., Baylink, D. J. and Lanyon, L. E. (2002), Human Osteoblasts' Proliferative Responses to Strain and 17β-Estradiol Are Mediated by the Estrogen Receptor and the Receptor for Insulin-Like Growth Factor I. J Bone Miner Res, 17: 593–602. doi: 10.1359/jbmr.2002.17.4.593
- Issue published online: 2 DEC 2009
- Article first published online: 1 APR 2002
- Manuscript Accepted: 15 NOV 2001
- Manuscript Revised: 26 MAR 2001
- Manuscript Received: 14 AUG 2000
- insulin-like growth factors;
- human osteoblast;
The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17β-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17β-estradiol occurred at 10−8-10−7 M and the peak response to strain occurred at 3500 microstrain (μϵ). Both strain-related and 17β-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10−8 M). Tamoxifen (10−9-10−8 M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17β-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17β-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 μg/ml) blocked the effects of 17β-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 μg/ml) blocked the effects of strain and tIGF-II but not those of 17β-estradiol or tIGF-I. MAb αIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17β-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17β-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17β-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17β-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.