The effects of triiodothyronine on human osteoblast-like cells metabolism and interactions with growth hormone.
The expression of thyroid hormones receptors in osteoblasts and osteoclasts has involved these cells as direct targets for triiodothyronine (T3), but thyroid hormones may also interact with other hormones or local growth factors to exert their actions on bone cells. Among these, growth hormone (GH) is recognised as participating in the acquisition and maintenance of bone mass and exerting stimulatory effects on human osteoblastic cells. The aim of this study was to investigate T3 effects on primary human adult osteoblast-like cells (HOB) as well as to test for possible interactions between T3 and GH on bone cell metabolism. Primary human bone cell cultures were obtained by outgrowth from trabecular bone fragments from the hip and knee. Dose-response studies demonstrated enhanced [3H]-thymidine incorporation for T3 at 10(-9), 10(-8), 10(-7) and 20(-7) M, with a maximal response of 162.81 +/- 12.97 % with T3 10(-8) M, compared to vehicle (p < 0.001). Time-course studies showed an increased osteoblast-like cell proliferation after 24 h, followed by a decrease of cell proliferation by 48 h and 72 h of culture, respectively, when compared to control cells, with a maximal response after 72 h (T3 10(-10) M: 45.21 +/- 6.97 %, p < 0.01). In addition, T3 markedly increased specific alkaline phosphatase (AP) activity in HOB (10(-10) M: 169.86 +/- 12.14 % vs. control, p < 0.001), but no significant influence on type I procollagen propeptide (PICP) production was observed. At 10(-9) - 10(-7) g/ml, GH significantly enhanced HOB proliferation (p < 0.001) however, GH effects were not dose-dependent. Triiodothyronine, at a high concentration (10(-7) M), stimulated GH-receptor (GHR) mRNA levels by 165.20 +/- 16.54 % after 24 h (p < 0.05). Correspondingly, a synergistic effect of T 3 with the same concentration and GH on cell proliferation in human adult osteoblast-like cells was found.
Department of Internal Medicine I, University of Heidelberg, Heidelberg, Germany. carmenpepene@yahoo.com
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Pepene
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Pfeilschifter
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Gozariu
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Kasperk
D000328:Adult; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D018076:DNA, Complementary; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D018076:DNA, Complementary; D011347:Procollagen; D012333:RNA, Messenger; D014284:Triiodothyronine; D019382:Human Growth Hormone; D004247:DNA; D013936:Thymidine