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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoids exert potent inhibitory effects on bone formation. We have previously shown that glucocorticoids suppress plasminogen activator (PA) activity in normal and malignant rat osteoblasts. To clarify the mechanism of this suppression, we investigated the effects of dexamethasone on PA inhibitor-1 (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) expression and also on PAI-1 protein and PA activity in both normal rat calvarial osteoblasts and a clonal osteogenic sarcoma cell line, UMR 106-01. Dexamethasone increased PAI-1 mRNA and protein in both cell types. The increase in PAI-1 protein and the decrease in PA activity were obtained over the same concentration range, with a half-maximally effective concentration of dexamethasone of about 10(-9) M. The increase in PAI-1 mRNA caused by dexamethasone was retained with cycloheximide treatment, but abolished with actinomycin-D. Dexamethasone had no effect on tPA or uPA mRNA in either cell type. The glucocorticoid antagonist RU 486 prevented the effects of dexamethasone on PA activity and PAI-1 protein. Dihydrotestosterone, progesterone, and 17 beta-estradiol did not influence PA activity or PAI-1 formation. Although tPA and uPA protein could not be measured, these results suggest that glucocorticoids suppress PA activity predominantly by increasing PAI-1 synthesis in rat osteoblasts. Suppression of PA activity through actions on PAI-1 formation by glucocorticoids could contribute to the mechanisms by which glucocorticoids inhibit bone formation.
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PMID:Glucocorticoid regulation of plasminogen activator inhibitor-1 messenger ribonucleic acid and protein in normal and malignant rat osteoblasts. 173 26

This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.
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PMID:Androgens directly stimulate proliferation of bone cells in vitro. 252 24

Previously, we showed that androgens stimulate murine and human osteoblast-like cell proliferation and differentiation by mechanisms involving increased responses to mitogenic growth factors (GF) and increased GF production. To explain this dual action of androgens on primary osteoblastic cell populations we advanced the hypothesis that androgens exert differential effects on osteoblastic subpopulations. We subcloned a human osteosarcoma cell line (SaOS2) into subpopulations expressing high (HAS) and low (LAS) levels of alkaline phosphatase (ALP). The obtained subclones differed significantly in their ALP production and expressed a high and low ALP phenotype, respectively, for the entire experimental period. Dihydrotestosterone (DHT) increased specific ALP activity and type-I procollagen peptide secretion in both HAS and LAS. DHT pretreatment enhanced the mitogenic action of basic fibroblast growth factor (bFGF) and insulinlike growth factor 2 (IGF2) only in HAS. The enhanced mitogenic effect of IGF2 in HAS after DHT pretreatment was associated with increased IGF2-receptor mRNA levels. Therefore, we conclude that androgens exert their osteoanabolic action (1) by stimulating differentiated functions of osteoblastic cells with a high and a low ALP phenotype, and (2) via increased growth factor receptor expression and thereby enhancing mitogenic growth factor responses only in HAS.
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PMID:Effects of androgens on subpopulations of the human osteosarcoma cell line SaOS2. 866 74