Co-culture of mechanically injured cartilage with joint capsule tissue alters chondrocyte expression patterns and increases ADAMTS5 production

Arch Biochem Biophys. 2009 Sep;489(1-2):118-26. doi: 10.1016/j.abb.2009.07.006. Epub 2009 Jul 14.

Abstract

We studied changes in chondrocyte gene expression, aggrecan degradation, and aggrecanase production and activity in normal and mechanically injured cartilage co-cultured with joint capsule tissue. Chondrocyte expression of 21 genes was measured at 1, 2, 4, 6, 12, and 24h after treatment; clustering analysis enabled identification of co-expression profiles. Aggrecan fragments retained in cartilage and released to medium and loss of cartilage sGAG were quantified. Increased expression of MMP-13 and ADAMTS4 clustered with effects of co-culture, while increased expression of ADAMTS5, MMP-3, TGF-beta, c-fos, c-jun clustered with cartilage injury. ADAMTS5 protein within cartilage (immunohistochemistry) increased following injury and with co-culture. Cartilage sGAG decreased over 16-days, most severely following injury plus co-culture. Cartilage aggrecan was cleaved at aggrecanase sites in the interglobular and C-terminal domains, resulting in loss of the G3 domain, especially after injury plus co-culture. Together, these results support the hypothesis that interactions between injured cartilage and other joint tissues are important in matrix catabolism after joint injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ADAM Proteins / biosynthesis*
  • Aggrecans / metabolism
  • Animals
  • Cartilage / injuries*
  • Cartilage / metabolism*
  • Cartilage / pathology
  • Cattle
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Coculture Techniques
  • Endopeptidases / metabolism
  • Gene Expression Regulation*
  • Joint Capsule / metabolism*
  • Joint Capsule / pathology
  • Matrix Metalloproteinase 13 / biosynthesis
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Time Factors
  • Transforming Growth Factor beta / biosynthesis

Substances

  • Aggrecans
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transforming Growth Factor beta
  • Endopeptidases
  • ADAM Proteins
  • Matrix Metalloproteinase 13
  • aggrecanase