Expression of the vitamin D receptor, of estrogen and thyroid hormone receptor α- and β-isoforms, and of the androgen receptor in cultures of native mouse bone marrow and of stromal/osteoblastic cells

Gruber, Reinhard; Czerwenka, K.; Wolf, Florian; Ho, Guan-Min; Willheim, Martin; Peterlik, Meinrad

doi:10.1016/s8756-3282(99)00017-4

Cited by 78 publications

(46 citation statements)

References 29 publications

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“…This is in agreement with some, but in disagreement with the results of others (10 -14, 37, 38). Most ER studies were performed in osteosarcoma cell lines, which are dedifferentiated into an embryonic state (13,14,36,37) or in bones of immature rats or individuals with healing fractures or various bone diseases (11). Indeed, in developing bones our quantitative real-time RT-PCR system picks up ERb mRNA readily (authors' unpublished data).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

Seidlová-Wuttke

Hesse²,

Jarry³

et al. 2003

European Journal of Endocrinology

125

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Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. In the present experiments, the effects of the clinically used Cimicifuga racemosa (CR) extract BNO 1055 in the uterus, in the bone and on serum luteinizing hormone (LH) were compared with the effects of estradiol-17b (E 2 ) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E 2 or the CR extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E 2 and the CR extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E 2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E 2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E 2 and partially by CR supplementation.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, in developing bones our quantitative real-time RT-PCR system picks up ERb mRNA readily (authors' unpublished data). Few publications indicate the presence of ERb in the bone of adult rats or mice (10,37,38). If ERb are present in adult bones their number is extremely low.…”

Section: Discussionmentioning

confidence: 99%

Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

Seidlová-Wuttke

Hesse²,

Jarry³

et al. 2003

European Journal of Endocrinology

125

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“…(6)(7)(8) Osteoblasts are potential targets for androgen action because they contain a high AR expression. (9)(10)(11) Thus far two osteoblastspecific AR knockouts have been generated. In these two models, both the osteoblast and the osteocyte were targeted, which resulted in a trabecular bone phenotype, confirming that the osteoblast and/or osteocyte is a target cell for AR-mediated maintenance of trabecular bone volume.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes

Sinnesael

Claessens

Laurent

et al. 2012

Journal of Bone and Mineral Research

102

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Androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling has been mainly attributed to osteoblasts. Although osteocytes have emerged as key regulators of bone remodeling, the influence of sex steroids on these cells has been poorly studied. We aimed to investigate the role of AR signaling, specifically in osteocytes using the Cre/LoxP system in male mice (driven by dentin matrix protein 1 [ocy-ARKOs]). Osteocyte fractions of control (AR(ex2)/Y) and ocy-ARKO (ARflox(ex2)/Y; DMP1-cre) mice isolated through sequential collagenase digestion showed increasing AR expression toward the mature osteocyte fraction of control males compared with the more immature fractions, whereas this was reduced by >80% in ocy-ARKO osteocytes. The skeletal phenotype of mutant mice was further assessed by histomorphometry and quantitative micro-computed tomography at 12 and 32 weeks of age. Ocy-ARKOs had significantly lower trabecular bone volume and number in femora and tibias at 32 weeks as well as decreased trabecular number in the L 5 vertebra at 12 weeks. Biomechanical testing showed that ocy-ARKO femora were also stiffer and required a lower ultimate force to induce failure at 32 weeks. However, femoral cortical structure was not significantly different at any time point. The absence of AR in osteocyte also did not appear to affect trabecular bone formation nor its response to mechanical loading. In conclusion, selective inactivation of the AR in osteocytes of male mice accelerates age-related deterioration of skeletal integrity. These findings provide evidence for a direct role of androgens in the maintenance of trabecular bone through actions of the AR in osteocytes. ß

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“…Um achado importante foi a identificação das isoformas α e β de receptores de hormônio tiroideano na medula óssea de camundongos, bem como em células do estroma da medula (23). A medula óssea é um componente extremamente importante para a fisiologia óssea, uma vez que contém células hematopoiéticas e estromais que, por sua vez, incluem células precursoras dos osteoclastos e osteoblastos, respectivamente.…”

Section: Expressão De Receptores De Hormônio Tiroideano Em Células Esunclassified

“…Demonstrou-se que TRs e VDRs, além de receptores de estrógeno e andrógeno, estão co-expressos na medula óssea de camundongos (23), o que é um pré-requisito para tal sinergismo. Estudos mostram que o T 3 aumenta, de forma permissiva, o efeito da VD na osteoclastogenese em um processo dependente da interleucina-6 (IL-6) (45), uma citocina que possui papel fundamental nesse processo.…”

Section: Efeitos Do Hormônio Tiroideano Nos Osteoclastosunclassified

O efeito molecular e estrutural do hormônio tiroideano no esqueleto

Gouveia¹

2004

Arq Bras Endocrinol Metab

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RESUMOO hormônio tiroideano é essencial para o desenvolvimento, maturação e metabolismo ósseos normais. Durante o desenvolvimento, a deficiência do hormônio tiroideano resulta em atraso na maturação do esqueleto e disgênese das epífises, resultando em redução do crescimento e anormalidades esqueléticas. O hormônio tiroideano também tem efeito no osso do adulto. A tirotoxicose é freqüentemente associada ao aumento do metabolismo ósseo e diminuição da massa óssea. Embora a importância do hormônio tiroideano no desenvolvimento e metabolismo ósseos seja clara, os mecanismos que medeiam os efeitos desse hormônio no tecido ósseo apenas começam a ser desvendados. O hormônio tiroideano pode atuar indiretamente no esqueleto, aumetando a secreção de hormônio do crescimento (GH) e insulin-like growth factor-1 (IGF-1); ou diretamente, modulando genes alvo via receptores nucleares específicos. Não se sabe, entretanto, se os principais efeitos do hormônio tiroideano no osso são resultado de ações diretas ou indiretas. Achados in vitro, tais como a presença de receptores de hormônio tiroideano (TR) e a indução de genes e proteínas em células esqueléticas pelo hormônio tiroideano, evidenciam a importância de ações diretas. Esta revisão tem como meta sumarizar os achados in vivo e in vitro relacionados aos efeitos do hormônio tiroideano no esqueleto. During development, thyroid hormone deficiency results in delayed skeletal maturation and epiphyseal dysgenesis, resulting in reduced growth and skeletal abnormalities. Thyroid hormone also has effects on bones of adults. Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. However, the mechanisms that mediate its effects on bone tissue are poorly understood. Thyroid hormone acts indirectly in the skeleton, by increasing the secretion of growth hormone and insulin-like growth factor-1; or directly, by modulating target genes via specific nuclear receptors. In vitro findings, such as the presence of thyroid receptors (TRs) and the induction of genes and proteins in skeletal cells by thyroid hormone, emphasize the importance of direct actions. The aim of this review is to summarize the in vivo and in vitro findings related to the effects of thyroid hormone on the skeleton.

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Expression of the vitamin D receptor, of estrogen and thyroid hormone receptor α- and β-isoforms, and of the androgen receptor in cultures of native mouse bone marrow and of stromal/osteoblastic cells

Cited by 78 publications

References 29 publications

Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes

O efeito molecular e estrutural do hormônio tiroideano no esqueleto

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