Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts.
Triiodothyronine (T3) increases bone resorption, but its effects on matrix metalloprotease (MMP) expression in bone are unknown. We tested the effects of T3 on collagenase-3 and gelatinase A and B expression in MC3T3 osteoblastic cells. T3 at 1 nM to 1 microM for 24-72 h increased collagenase-3 and gelatinase B mRNA levels, but it did not increase gelatinase A transcripts. In addition, T3 increased immunoreactive collagenase and gelatinase activity. Cycloheximide prevented the stimulatory effect of T3 on collagenase-3 but not on gelatinase B transcripts. Indomethacin did not prevent the effect of T3 on either MMP. T3 did not alter the decay of collagenase-3 or gelatinase B mRNA in transcriptionally arrested MC3T3 cells, and it increased the rate of collagenase-3 and gelatinase B gene transcription. Although T3 enhanced the expression of the tissue inhibitor of metalloproteinase-1 in MC3T3 cells, it increased collagen degradation in cultured intact rat calvariae. In conclusion, T3 increases collagenase-3 and gelatinase B synthesis in osteoblasts by transcriptional mechanisms. This effect may contribute to the actions of T3 on bone matrix remodeling.
Pereira
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RC
Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford 06105, Connecticut, USA.
Jorgetti
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V
Canalis
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D016475:3T3 Cells; D000818:Animals; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology*
D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D014284:Triiodothyronine; D003513:Cycloheximide; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat; D020780:Matrix Metalloproteinase 9