Abstract:
: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.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Varghese S,Canalis Edoi
10.1002/jcb.10732subject
Has Abstractpub_date
2003-12-01 00:00:00pages
1007-14issue
5eissn
0730-2312issn
1097-4644journal_volume
90pub_type
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