Regulation of tumor necrosis factor-alpha and tumor necrosis factor converting enzyme in human osteoarthritis.

Abstract

A snake venom-like protease isolated by a differential display screen between normal and osteoarthritis (OA)-affected cartilage (designated as cSVP) has a cDNA sequence identical to tumor necrosis factor (TNF)alpha convertase enzyme (TACE) and belongs to the adamalysin group of proteases. It has unique structural properties and when expressed in baculovirus, cleaves preferentially proTNFalpha to TNFalpha. The OA-affected cartilage has upregulated mRNA for TNFalpha and TACE as compared to normal cartilage. TNFalpha and TACE regulate inflammatory mediators in OA-affected cartilage which can be inhibited by both soluble TNFalpha receptors and inhibitors of TACE. These experiments demonstrate a functional paracrine/autocrine role of TNFalpha in OA-affected cartilage that is modulated by upregulated levels of chondrocyte-derived TACE.

• Authors: A R Amin
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 7 Issue 4 Pg. 392-4 (Jul 1999) ISSN: 1063-4584 [Print] England
• PMID: 10419777 (Publication Type: Journal Article)
• Copyright: Copyright 1999 OsteoArthritis Research Society International.

Chemical References

• Interleukin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Prostaglandin-Endoperoxide Synthases
• ADAM Proteins
• Metalloendopeptidases
• ADAM17 Protein
• ADAM17 protein, human

Topics

• ADAM Proteins
• ADAM17 Protein
• Chondrocytes (metabolism)
• Humans
• Interleukin-1 (metabolism)
• Metalloendopeptidases (physiology)
• Osteoarthritis (etiology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• RNA, Messenger (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)