Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells

Mizuno, Yoshifumi; Hosoi, Takayuki; Inoue, Satoshi; Ikegami, Akira; Kaneki, Masao; Akedo, Yoko; Nakamura, Takashi; Ouchi, Yasuyoshi; Chang, Chawnshang; Orimo, Hajime

doi:10.1007/bf00295958

Cited by 82 publications

(43 citation statements)

References 18 publications

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“…These findings have since been confirmed by other groups using a variety of osteoblastic cell systems from various species (31)(32)(33)(34)(35)(36). Functional AR were also detected in pluripotent marrow-derived stromal cells (19), which represent osteoblast precursor cells, hypertrophic chondrocytes (20), osteocytes (20) as well as osteoclasts (21). The detection of functional AR in various bone cells has implicated bone as a target tissue for androgen action and has fueled an increase in further investigations on the direct and indirect effects of androgens on bone cells in vitro, as well as the sequelae of clinical and experimental androgen deficiency and its correction on bone metabolism in vivo.…”

Section: Bone As Direct Androgen Targetdetection Of the Ar In Bone Cellssupporting

confidence: 67%

“…The cloning of the human androgen receptor (AR) (16,17) and its detection and characterization in various bone cells, including osteoblasts (18), bone marrow-derived stromal cells (19), osteocytes (20), hypertrophic chondrocytes (20), and osteoclasts (21), have unequivocally identified bone as a direct androgen target tissue. In addition, subsequent studies over the last decade have identified a variety of androgen-dependent autocrine and paracrine cytokines which are produced by bone cells and mediate some of the anabolic and anti-resorptive effects of androgens.…”

Section: Introductionmentioning

confidence: 99%

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Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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Androgens have beneficial effects on skeletal development and maintenance in women and men. The detection and functional characterization of androgen receptors in bone cells has implicated bone tissue as a potential target tissue for androgens. Gonadal and adrenal androgens directly regulate various aspects of osteoblastic lineage cells, including proliferation, differentiation, mineralization, and gene expression. These effects may differ depending on the stage of differentiation, the number of androgen receptors, and other inherent characteristics (species, site, cell biology) of the osteoblastic cell system. In addition, recent studies have suggested that some of the anabolic and anti-resorptive effects of androgens on bone may be mediated by regulation of autocrine and paracrine factors in the bone microenvironment, including transforming growth factor-b, insulin-like growth factors (and their binding proteins), and interleukin-6. This review summarizes the recent progress made in our knowledge of androgen receptor action, local androgen metabolism in bone, and direct and indirect effects of gonadal and adrenal androgens as well as androgen receptor antagonists on bone cells.

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Section: Bone As Direct Androgen Targetdetection Of the Ar In Bone Cellssupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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“…In the cartilage and bone, AR is expressed in chondrocytes, osteoblasts, osteocytes (15), and osteoclasts (16). Clinical studies suggested that combined therapy of estrogens plus androgens may enhance bone mineral density and bone mass to a more significant degree than estrogen therapy alone in postmenopausal women (17,18).…”

mentioning

confidence: 99%

Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

Yeh

Tsai

et al. 2002

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

602

456

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By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice

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“…AR expression has been shown in a number of bone cells including pluripotent mesenchymal bone marrow stromal cells, osteoblasts, osteoclasts and osteocytes. (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.…”

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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Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells

Cited by 82 publications

References 18 publications

Androgen effects on bone metabolism: recent progress and controversies

Androgen effects on bone metabolism: recent progress and controversies

Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

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

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