Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage

J Cell Biochem. 2002;85(2):295-303. doi: 10.1002/jcb.10138.

Abstract

Tissue inhibitor of metalloproteinases-4 (TIMP-4), the newest member of the TIMP family, blocks the activities of several matrix metalloproteinases (MMPs) implicated in the arthritic cartilage erosion. By utilizing semi-quantitative RT-PCR, immunoblotting, and immunohistochemistry, we investigated whether the TIMP-4 gene is expressed in human non-arthritic and osteoarthritic (OA) cartilage. Directly analyzed femoral head cartilage showed TIMP-4 RNA expression in 2 of 9 non-arthritic and 12 of 14 OA patients. Femoral head cartilage from 6 of 9 OA patients had elevated TIMP-4 protein compared to the low-level expression in 3 of 8 non-arthritic controls. In most patients, there was correlation between TIMP-4 RNA and protein expression. TIMP-4 protein was also detected immunohistochemically in the upper zone of OA cartilage. The widespread TIMP-4 RNA and protein expression and augmentation in femoral OA cartilage suggests its important role in joint tissue remodeling and pathogenesis of OA. Increased TIMP levels in arthritic cartilage may not be a sufficiently effective defense against cartilage resorption by excessive multiple MMPs and aggrecanases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Cartilage / enzymology*
  • Chondrocytes / metabolism
  • DNA Primers / chemistry
  • Female
  • Femur Head / enzymology*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Osteoarthritis, Hip / enzymology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-4
  • Tissue Inhibitor of Metalloproteinases / genetics*
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • DNA Primers
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases