Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17β-estradiol

Gregorio, Gina B. Di; Yamamoto, Masahide; Ali, Arshad; Abe, Etsuko; Roberson, Paula K.; Manolagas, Stavros C.; Jilka, Robert L.

doi:10.1172/jci11653

Cited by 121 publications

(119 citation statements)

References 54 publications

(44 reference statements)

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“…The effect of the loss of estrogens on the rate of remodeling and the up-regulation of osteoblastogenesis and bone formation in animals and humans, however, wanes with time (5-10 years in women and 6 -8 weeks in mice) raising the possibility that aging might be overriding the acute effects of estrogen deficiency. Considering the evidence that unopposed oxidative stress promotes premature hematopoietic stem cell differentiation, it is possible that following acute loss of estrogens, the increased ROS levels in MSCs may promote their exit from quiescence, replication, and development of transit amplifying osteoblast progenitors, the latter already confirmed by our earlier work (45). These mechanisms, lead to up-regulation of osteoblast differentiation and thereby increased bone formation.…”

Section: Discussionsupporting

confidence: 62%

Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription

Almeida

Han

Martin-Millan

et al. 2007

Journal of Biological Chemistry

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472

394

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We have elucidated that oxidative stress is a pivotal pathogenetic factor of age-related bone loss and strength in mice, leading to, among other changes, a decrease in osteoblast number and bone formation. To gain insight into the molecular mechanism by which oxidative stress exerts such adverse effects, we have tested the hypothesis that induction of the Forkhead box O (FoxO) transcription factors by reactive oxygen species may antagonize Wnt signaling, an essential stimulus for osteoblastogenesis. In support of this hypothesis, we report herein that the expression of FoxO target genes increases, whereas the expression of Wnt target genes decreases, with increasing age in C57BL/6 mice. Moreover, we show that in osteoblastic cell models, oxidative stress (exemplified by H 2 O 2 ) promotes the association of FoxOs with ␤-catenin, ␤-catenin is required for the stimulation of FoxO target genes by H 2 O 2 , and H 2 O 2 promotes FoxO-mediated transcription at the expense of Wnt-/T-cell factor-mediated transcription and osteoblast differentiation. Furthermore, ␤-catenin overexpression is sufficient to prevent FoxO-mediated suppression of T-cell factor transcription. These results demonstrate that diversion of the limited pool of ␤-catenin from T-cell factor-to FoxO-mediated transcription in osteoblastic cells may account, at least in part, for the attenuation of osteoblastogenesis and bone formation by the age-dependent increase in oxidative stress.

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Section: Discussionsupporting

confidence: 62%

Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription

Almeida

Han

Martin-Millan

et al. 2007

Journal of Biological Chemistry

Self Cite

472

394

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“…Cell Culture-Bone marrow cells were harvested from long bones and used to quantify colony forming units (CFU)-fibroblast (CFU-F) and CFU-osteoblasts (CFU-OB) as previously described (27). Osteoblast differentiation of bone marrow precursors was evaluated by plating bone marrow cells in 12-well plates at 5 ϫ 10 6 cells/well and culturing in ␣-MEM containing 15% fetal bovine serum, 1% penicillin/streptomycin/glutamine, 1% ascorbic acid, and 10 mM ␤-glycerolphosphate.…”

Section: Methodsmentioning

confidence: 99%

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging

Onal

Piemontese

Xiong

et al. 2013

Journal of Biological Chemistry

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175

144

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“…It also attenuates the self renewal of early osteoblast progenitors (having limited self-renewal capacity) for both osteoblasts and osteoclasts. Both these effects slow down bone remodeling (104,105). Through TGF β, estrogen causes repression of T cell proliferation and differentiation, and inhibits INFγ production.…”

Section: Osteogenic Progenitorsmentioning

confidence: 99%

Sex Steroids and Stem Cell Function

Ray

Novotny

Crisostomo

et al. 2008

Mol Med

104

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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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Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17β-estradiol

Cited by 121 publications

References 54 publications

Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription

Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging

Sex Steroids and Stem Cell Function

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