Transcriptional regulation of collagenase-3 by interleukin-1 alpha in osteoblasts.
Interleukin-1 (IL-1)alpha is an autocrine/paracrine agent of the skeletal tissue and it regulates bone remodeling. Collagenase-3 or matrix metalloproteinase (MMP)-13 is expressed in osteoblasts and its expression is modulated by several cytokines including IL-1alpha. Because the molecular mechanism of increased synthesis of collagenase-3 in bone cells by IL-1alpha is not known, we investigated if collagenase-3 expression by IL-1alpha in osteoblasts is mediated by transcriptional or post-transcriptional mechanisms. Exposure of rat osteoblastic cultures (Ob cells) to IL-1alpha at concentrations higher than 0.5 nM increased the synthesis of collagenase-3 mRNA up to eightfold and the secretion of immunoreactive protein up to 21-fold. The effects of IL-1alpha on collagenase-3 were time- and dose-dependent. Although prostaglandins stimulate collagenase-3 expression, stimulation of collagenase-3 in Ob cells by IL-1alpha was not mediated through increased biosynthesis of prostaglandins. The half-life of collagenase-3 mRNA from control and IL-1alpha-treated Ob cells was similar suggesting that the stabilization of collagenase-3 mRNA did not contribute to the increase in collagenase-3. However, IL-1alpha stimulated the rate of transcription of the collagenase-3 gene by twofold to fourfold indicating regulation of collagenase-3 expression in Ob cells at the transcriptional level. Stimulation of collagenase-3 by IL-1alpha in osteoblasts may in part mediate the effects of IL-1alpha in bone metabolism.
Varghese
Samuel
S
The Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA. svarghes@stfranciscare.org
Canalis
Ernesto
E
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006207:Half-Life; D007375:Interleukin-1 / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010294:Parietal Bone / Q000737:chemistry; D011453:Prostaglandins / Q000378:metabolism; D020871:RNA Stability; D051381:Rats; D014158:Transcription, Genetic
D007375:Interleukin-1; D011453:Prostaglandins; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat