Enhanced osteoblast proliferation and collagen gene expression by estradiol.

Ernst, Matthias; Schmid, Christoph; Froesch, E. R.

doi:10.1073/pnas.85.7.2307

Cited by 194 publications

(82 citation statements)

References 23 publications

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“…The question arises of whether decreased longitudinal growth could contribute to the increased Although estrogen clearly has a potent antiresorptive effect, which has made a separate anabolic effect difficult to identify, it seems reasonable that a hormone implicated in the maintenance ofbone mass should be both anabolic and anticatabolic. In fact, there is evidence from other sources that supports an anabolic role for estrogen: ovariectomy in Beagle dogs has been found to reduce mean wall thickness (21), and estrogen increases proliferation and collagen production by bone cells in vitro (22,23).…”

Section: Discussion One Tormationmentioning

confidence: 99%

Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation.

Chow¹,

Tobias²,

Colston³

et al. 1992

J. Clin. Invest.

245

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Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacologic doses of estrogen increases bone formation in ovary-intact rats. To assess the effects of physiological concentrations of estrogen on bone formation, estrogen was administered to ovariectomized rats in which bone resorption was suppressed by the bisphosphonate 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP). Animals receiving exogenous 170t-estradiol (E2) (1, 10, and 100 ,g/kg daily for 17 d) showed a dose-dependent increase in trabecular bone volume of 1.9, 25.8, and 43.6%, respectively, compared with those rats treated with AHPrBP alone. The increase in bone volume was associated with an increase in bone formation in E2-treated animals, in which bone resorption had been almost completely suppressed by AHPrBP. Neither ovariectomy, AHPrBP, nor E2 treatment had a significant effect on the volume or rate of formation of cortical bone. Thus, the increased bone resorption, which is a consequence of estrogen-deficiency, entrains increased bone formation, which masks a simultaneous reduction in estrogendependent bone formation. Therefore, in addition to the nonspecific effect of estrogen to depress formation via coupling, we have identified a specific effect of estrogen to increase formation independent of coupling. Thus it appears that estrogen maintains bone volume not only through inhibition of bone resorption, but also through stimulation of bone formation. (J.

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Section: Discussion One Tormationmentioning

confidence: 99%

Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation.

Chow¹,

Tobias²,

Colston³

et al. 1992

J. Clin. Invest.

245

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“…Both specific nuclear binding of estradiol and the presence of estrogen receptor mRNA were demonstrated in normal human osteoblast-like cell strains (13) and in rat and human osteogenic sarcoma cell lines (14). Moreover, biologic effects of estrogen treatment in vitro have been demonstrated on proliferation and differentiation of normal mouse osteoblast-like cells (15) and rat osteogenic sarcoma cell lines (16), on induction of progesterone receptors in human osteoblastlike cell strains (13), and on induction of gene transcription for type I procollagen and transforming growth factor P3 in rat and human osteogenic sarcoma cell lines (14).…”

mentioning

confidence: 89%

Identification of androgen receptors in normal human osteoblast-like cells.

Colvard

Eriksen

Keeting

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

420

144

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The sex steroids, androgens and estrogens, are major regulators of bone metabolism. However, whether these hormones act on bone cells through direct or Androgens and estrogens are major regulators of bone metabolism in males and females, respectively (1). Both hormones interact with growth hormone in control of the adolescent growth spurt (2-4). After growth is completed, androgens and estrogens maintain bone mass in the adult. In women, menopause causes accelerated bone loss that can be prevented by estrogen administration (5,6). Treatment of postmenopausal women with androgen derivatives, synthetic anabolic steroids, produces beneficial effects on bone metabolism (7, 8). In males, hypogonadism is associated with bone loss, which is stabilized by testosterone administration (9).Because previous attempts to demonstrate receptors in bone cells of experimental animals (10, 11) or humans (12) have been unsuccessful, the prevailing view has been that the action of sex steroids on skeletal tissue is mediated indirectly. Recent data, however, suggest that estrogen has a direct action. Both specific nuclear binding of estradiol and the presence of estrogen receptor mRNA were demonstrated in normal human osteoblast-like cell strains (13) (17,18). In addition, a cDNA probe for the human androgen receptor (19) was used to determine whether human osteoblasts contained androgen receptor mRNA. METHODSCell Culture. Human bone cells were cultured from fresh samples of trabecular bone obtained during orthopedic procedures, by a procedure modified from that developed by Robey and Termine (20). These cultured cells had the typical characteristics of the osteoblast phenotype (13, 21). In brief, residual fibrous tissue was carefully dissected from the bone samples, which were then washed and minced in phosphatebuffered saline and digested with crude bacterial collagenase (GIBCO) at 1 mg/ml in Dulbecco's modified Eagle's medium (DMEM, GIBCO) for 2 hr at 370C in a shaking water bath. These fragments were then cultured in a phenol red-free medium (GIBCO) approximately equivalent to a Ca2+-free 1:1 (vol/vol) mixture of Ham's F-12 and DMEM supplemented with 10% heat-inactivated fetal bovine serum and penicillin/streptomycin. Steroid receptor assays were routinely performed after the second passage of cells in 175-cm2 culture flasks (20-30 population doublings). Two to 3 months of culture were required to obtain the 4 million cells needed for each assay in replicate.In experiments to assess nuclear binding of radiolabeled steroids, the medium was replaced for 48 hr by the same medium containing 20% fetal bovine serum and 2 mM Ca2'.Twenty-four hours before receptor assay, the medium was changed to serum-free medium containing 2 mM Ca2 .Nuclear Binding Assay. The specific nuclear binding of tritiated steroids in these cells was measured by a nuclear binding assay as described in detail previously and modified for tissue culture cells (13,17,18). In brief, human osteoblastlike cells at confluence were removed by trypsinization and...

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“…Res. bone. Osteoblasts have been shown to have estrogen receptors (8,9), and the addition of estrogens to bone cell lines has been shown to have functional effects (10)(11)(12) including the synthesis of growth factors such as transforming growth factor A and insulin-like growth factors I and 11 (13)(14)(15). These findings demonstrate that estrogens act directly on bone.…”

Section: Introductionmentioning

confidence: 55%