Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage.
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.
Huang
Wensheng
W
Departments of Medicine, Research Center and Notre-Dame Hospital of the Centre hospitalier de l'université de Montréal (CHUM), Montreal, Quebec, Canada H2L 4M1.
Li
Wen Qing
WQ
Dehnade
Faramaze
F
Zafarullah
Muhammad
M
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002356:Cartilage / Q000201:enzymology*; D019902:Chondrocytes / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005270:Femur Head / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
D017931:DNA Primers; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4