Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

BMC Musculoskelet Disord. 2011 Jul 15;12:164. doi: 10.1186/1471-2474-12-164.

Abstract

Background: Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes in vitro. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.

Methods: TN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.

Results: TN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE2, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.

Conclusions: TN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Cattle
  • Cell Line, Tumor
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Chondrocytes / pathology*
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Female
  • Humans
  • Inflammation Mediators / metabolism*
  • Inflammation Mediators / physiology
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / etiology
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Rats
  • Rats, Inbred Lew
  • Synovial Fluid / metabolism
  • Tenascin / biosynthesis
  • Tenascin / genetics
  • Tenascin / physiology*
  • Up-Regulation / physiology

Substances

  • Inflammation Mediators
  • Tenascin