Androgens Directly Stimulate Mineralization and Increase Androgen Receptors in Human Osteoblast-like Osteosarcoma Cells

Takeuchi, Masaharu; Kakushi, Hisato; Tohkin, M

doi:10.1006/bbrc.1994.2545

Cited by 65 publications

(40 citation statements)

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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).…”

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

confidence: 66%

“…In TE-85 osteosarcoma cells, 5a-DHT increased mineralization of extracellular bone matrix as assessed by calcium incorporation in a time-and dose-dependent fashion (35). Consistent with this, Kasperk et al (99) demonstrated that both 5a-DHT and DHEA stimulated mineralization of extracellular matrix by primary human osteoblastic cells.…”

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

confidence: 71%

“…Using the hFOB/ AR-6 cell line, 5a-DHT inhibited both baseline and 1,25-dihydroxyvitamin D 3 -induced type I collagen synthesis in a dose-dependent manner (44). Osteocalcin secretion has been reported to be stimulated (99) or not affected (35,44) by androgens.…”

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

confidence: 98%

“…5a-Dihydrotestosterone (5a-DHT) has been demonstrated to up-regulate AR expression (35) and transcriptional activation in osteoblastic cells (45). In addition, dexamethasone, 1,25-dihydroxyvitamin D 3 , and 17b-estradiol have also been demonstrated to increase AR mRNA steady state levels (37).…”

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

confidence: 99%

“…However, the significance of this observation was dampened by the fact that the percentage of AP-positive cells was suboptimal (and therefore not all of the cells were truly mature osteoblasts) and that AP-negative cells could potentially represent non-osteoblastic cell populations derived from the preparation procedure. Subsequently, AP activity of osteoblasts was shown to be increased (99), not affected (35,102), or decreased (44) by various androgens. DHEA and 5a-DHT were similar in stimulating both the percentage of AP-positive cells and AP activity by primary human osteoblastic cells, without prior conversion of DHEA and its metabolites by 3b-hydroxysteroid dehydrogenase or 5a-reductase (99).…”

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

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: 66%

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

confidence: 71%

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

confidence: 98%

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

confidence: 99%

Section: Effects Of Androgens On Osteoblast Differentiationmentioning

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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Testosterone Therapy in Glucocorticoid-Treated Men

Reid¹

1996

Arch Intern Med

318

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Development and characterization of a conditionally immortalized human osteoblastic cell line stably transfected with the human androgen receptor gene

et al. 1997

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Androgens have significant beneficial effects on the skeleton. However, studies on the effects of androgens on osteoblasts are limited due to the absence of appropriate model systems that combine completeness of the osteoblastic phenotype, rapid proliferation rate, and stable expression of the androgen receptor (AR). Thus, we stably transfected the conditionally immortalized human fetal osteoblastic cell line (hFOB) with the human wild-type AR (hAR) cDNA. Compared to nontransfected hFOB cells, constitutive hAR mRNA expression in three independent hAR-transfected hFOB clones (hFOB/AR) was 15-fold higher in hFOB/AR-16, 62-fold higher in hFOB/AR-2, and 72-fold higher in hFOB/AR-6 cells, respectively, as assessed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Detectable constitutive levels of hAR mRNA by Northern blot analysis were present in hFOB/AR-2 and hFOB/AR-6 cells, but not in hFOB/AR-16 or hFOB cells, respectively. Treatment with 5 alpha-dihydrotestosterone (5 alpha-DHT) (10(-8) M) for 24 h did not alter hAR mRNA steady state levels in the hFOB/AR cell lines. Nuclear binding studies demonstrated 152 +/- 73 (mean +/- SEM) functional hARs/nucleus in non-transfected hFOB cells, 3,940 +/- 395 functional hARs/nucleus in hFOB/AR-2 cells, and 3,987 +/- 823 hARs/nucleus in hFOB/AR-6 cells, respectively. Treatment with 5 alpha-DHT increased the expression of a transiently transfected androgen response element-chloramphenicol acetyltransferase (ARE-CAT) reporter construct in hFOB/AR-6 cells in a dose- and time-dependent manner; no such effect was observed in transiently transfected hFOB cells lacking exogenously transfected hARs. Moreover, 5 alpha-DHT-induced ARE-CAT expression was inhibited by the selective androgen receptor antagonist, hydroxyflutamide. In summary, we have developed and characterized androgen-responsive osteoblastic cell lines derived from normal human fetal bone that express physiological levels of functional hARs. These cell lines should provide a suitable model for further studies on the effects of androgens on osteoblast function, including the identification of potential androgen-regulated growth factors and cytokines.

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Androgens Directly Stimulate Mineralization and Increase Androgen Receptors in Human Osteoblast-like Osteosarcoma Cells

Cited by 65 publications

References 0 publications

Androgen effects on bone metabolism: recent progress and controversies

Androgen effects on bone metabolism: recent progress and controversies

Testosterone Therapy in Glucocorticoid-Treated Men

Development and characterization of a conditionally immortalized human osteoblastic cell line stably transfected with the human androgen receptor gene

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