Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells

Qi, Wang; Yu, Jinhua; Zhai, Huihong; Zhao, Qing-tao; Chen, Jinwu; Shu, Lei; Li, Deqiang; Liu, Dayong; Chen, Dong; Ding, Yin

doi:10.1016/j.bbrc.2006.06.070

Cited by 43 publications

(21 citation statements)

References 34 publications

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“…Estrogen signals mainly through estrogen receptors, which have been identified in cells of the osteoblast lineage, (23) as well as MSCs. (24) Although purely speculative, the persisting effect of 17-b estradiol after discontinuation could indicate irreversible differentiation toward osteoblasts, which have a typical lifespan of approximately 3 months.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Effect of Estrogen on Human Bone Marrow Fat

Limonard

Veldhuis-Vlug

Dussen

et al. 2015

Journal of Bone and Mineral Research

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Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p ¼ 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04) during the luteal phase (p ¼ 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17-b estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17-b estradiol administration (p < 0.001) and increased again after cessation. During 17-b estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p ¼ 0.034) and the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17-b estradiol rapidly reduces the marrow fat fraction, suggesting that 17-b estradiol regulates bone marrow fat independent of bone mass.

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Section: Discussionmentioning

confidence: 99%

Short-Term Effect of Estrogen on Human Bone Marrow Fat

Limonard

Veldhuis-Vlug

Dussen

et al. 2015

Journal of Bone and Mineral Research

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“…Earlier evidence showed that osteoblasts may control some aspects of ER␣ activation locally within bone. Some studies revealed greater ER␣ expression in parallel with osteoblast differentiation (24,25), although no evidence correlated this with an increase in ER␣-dependent function. Other studies showed that osteoblasts can metabolize various substrates into potent ER␣ agonists through endogenous aromatase (21) or 3-ketoreductase (20) activities or inactivate some ER␣ agonists through endogenous 3-hydroxysteroid dehydrogenase expression (3).…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, osteoblasts from fetal rat bone express little functional sex steroid receptor but acquire the ability to drive complex direct and indirect responses after transgenic receptor expression (3,12,20,22,23). Still, some studies suggest that endogenous estrogen receptor ␣ (ER␣) levels increase during late-stage osteoblast differentiation (24,25). To address this further, we investigated whether osteoblasts acquire a functional sex steroid response during differentiation in vitro.…”

mentioning

confidence: 99%

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

McCarthy

Clough²,

Gundberg³

et al. 2008

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

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Osteoblasts respond in direct and indirect ways to estrogens, and age-dependent changes in hormone levels and bone health can be limited by focused hormone replacement therapy. In this study, we report the release and isolation of an estrogen receptor agonist from osteoblast cultures. This entity reprises many aspects of estradiol activity in isolated osteoblasts, but differs from authentic estradiol by several biochemical and physical criteria. At levels that occur in conditioned medium from differentiating osteoblast cultures, the agonist directly drives gene expression through estrogen-sensitive response elements, activates the obligate osteoblast transcription factor Runx2, and potently enhances Smad-dependent gene expression in response to TGF-␤, but exhibits relatively lesser suppressive effects on gene expression through C/EBP and AP-1-binding protein transcription factors. Estrogen receptor agonist activity is resistant to heating at 100°C and separable from the bulk of the remaining alcohol-and hexane-soluble molecules by C18 chromatography. MS and molecular fragmentation analyses predict a Mr of 415.2 to 437.2. Therefore, in addition to earlier studies showing that osteoblasts readily respond to and metabolize various sex steroid-like substrates, we find that they also generate a potent estrogen receptor agonist during differentiation in vitro. Changes in the availability of a molecule like this within bone may relate to differences in skeletal integrity with aging or metabolic disease.intracrine ͉ selective estrogen receptor modulator ͉ steroid S ex steroids cause direct genomic transcriptional effects through specific receptors that contain ligand binding, dimerization, DNA binding, and gene transactivation domains. They also cause indirect stimulatory or inhibitory effects through complexes composed of activated hormone receptor and other transcription factors or through variations in the activation potential of other transcriptional components (1-6) The skeleton is a well recognized target for sex steroids. Bone fragility is notable when sex steroid levels fall in women after menopause, in elderly males, or after sex organ ablation (7-11). In such cases, bone loss follows a release from native constraints on bone resorption that largely result from changes in growth regulators expressed by osteoblasts and from opposing effects on osteoblast and osteoclast activation and apoptosis, leading to an overall increase in bone remodeling (12-16). Importantly, imbalances in bone remodeling are restored by sex hormone replacement therapy. Regardless of a clear benefit for bone, use of native sex steroids risks inappropriate gene activation in other tissues. The possibility of breast, cardiovascular, and prostate disease that can occur in this context (17-19) has driven the search for sex hormone receptor modulators with tissue-or function-restricted effects. However, the value of agents like these may be complicated by steroid and precursor metabolizing enzymes expressed by osteoblasts (3,20,21).Many cells u...

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“…Regarding the role of estrogens in osteogenic differentiation of MSCs, there is evidence that 17β-estradiol supports growth and differentiation mostly through the ERα receptor (49). This receptor bias may be attributed to interindividual variability and gender differences of osteoblast responses of MSCs to estrogen manifested by ERα polymorphism.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Sex Steroids and Stem Cell Function

Ray

Novotny

Crisostomo

et al. 2008

Mol Med

103

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Gender dimorphisms exist in the pathogenesis of a variety of cardiovascular, cardiopulmonary, neurodegenerative, and endocrine disorders. Estrogens exert immense influence on myocardial remodeling following ischemic insult, partially through paracrine growth hormone production by bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells. Estrogens also facilitate the mobilization of endothelial progenitor cells to the ischemic myocardium and enhance neovascularization at the ischemic border zone. Moreover, estrogens limit pathological myocardial remodeling through the inhibitory effects on the proliferation of the cardiac fibroblasts. Androgens also may stimulate endothelial progenitor cell migration from the bone marrow, yet the larger role of androgens in disease pathogenesis is not well characterized. The beneficial effects of sex steroids include alteration of lipid metabolism in preadipocytes, modulation of bone metabolism and skeletal maturation, and prevention of osteoporosis through their effects on osteogenic precursors. In an example of sex steroid-specific effects, neural stem cells exhibit enhanced proliferation in response to estrogens, whereas androgens mediate inhibitory effects on their proliferation. Although stem cells can offer significant therapeutic benefits in various cardiovascular, neurodegenerative, endocrine disorders, and disorders of bone metabolism, a greater understanding of sex hormones on diverse stem cell populations is required to improve their ultimate clinical efficacy. In this review, we focus on the effects of estrogen and testosterone on various stem and progenitor cell types, and their relevant intracellular mechanisms.

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Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells

Cited by 43 publications

References 34 publications

Short-Term Effect of Estrogen on Human Bone Marrow Fat

Short-Term Effect of Estrogen on Human Bone Marrow Fat

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

Sex Steroids and Stem Cell Function

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