title: Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I.
abstract: 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 17beta-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17beta-estradiol occurred at 10(-8) - 10(-7) M and the peak response to strain occurred at 3500 microstrain ((mu)epsilon). Both strain-related and 17beta-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 17beta-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 17beta-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 microg/ml) blocked the effects of 17beta-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 microg/ml) blocked the effects of strain and tIGF-II but not those of 17beta-estradiol or tIGF-I. MAb aIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17beta-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 17beta-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 17beta-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 17beta-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.
authors.affiliation: The Royal Veterinary College, University of London, United Kingdom.
authors.forename: Ming Zhao
authors.initials: MZ
authors.lastname: Cheng
authors.forename: Simon C F
authors.initials: SC
authors.lastname: Rawlinson
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pitsillides
authors.forename: Gul
authors.initials: G
authors.lastname: Zaman
authors.forename: Subburaman
authors.initials: S
authors.lastname: Mohan
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: Lance E
authors.initials: LE
authors.lastname: Lanyon
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000276:immunology / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013314:Stress, Mechanical; D013629:Tamoxifen / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D013936:Thymidine