Transcriptional regulation of collagenase-3 by interleukin-1 alpha in osteoblasts

✍ Scribed by Samuel Varghese; Ernesto Canalis

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 173 KB
• Volume: 90
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10732

✦ Synopsis

Abstract

Interleukin‐1 (IL‐1)α 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‐1α. Because the molecular mechanism of increased synthesis of collagenase‐3 in bone cells by IL‐1α is not known, we investigated if collagenase‐3 expression by IL‐1α in osteoblasts is mediated by transcriptional or post‐transcriptional mechanisms. Exposure of rat osteoblastic cultures (Ob cells) to IL‐1α 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‐1α on collagenase‐3 were time‐ and dose‐dependent. Although prostaglandins stimulate collagenase‐3 expression, stimulation of collagenase‐3 in Ob cells by IL‐1α was not mediated through increased biosynthesis of prostaglandins. The half‐life of collagenase‐3 mRNA from control and IL‐1α‐treated Ob cells was similar suggesting that the stabilization of collagenase‐3 mRNA did not contribute to the increase in collagenase‐3. However, IL‐1α 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‐1α in osteoblasts may in part mediate the effects of IL‐1α in bone metabolism. © 2003 Wiley‐Liss, Inc.