Up-regulation of cartilage oligomeric matrix protein at the onset of articular cartilage degeneration in a transgenic mouse model of osteoarthritis

Objective. To investigate the suitability of cartilage oligomeric matrix pr otein (COMP) as a marker for articular cartilage degeneration in a transgen ic mouse model of osteoarthritis (OA). Methods. Northern blot analysis of total RNA extracted from the knee joints of transgenic Del1 mice, which harbor a short deletion in a type II collag en transgene, and of their nontransgenic littermates was used to monitor ch anges in COMP messenger RNA (mRNA) levels during cartilage degeneration. Im munohistochemistry was used to determine the distribution of COMP in articu lar cartilage, and serum levels of COMP were measured by immunoassay. Results. Transient up-regulation of COMP mRNA was seen in articular cartila ge of transgenic Del1 mice at the onset of OA lesions at the age of 3 month s. Compared with nontransgenic controls, COMP immunostaining of articular c artilage in 3-9-month-old transgenic mice was increased, especially at the border of uncalcified and calcified cartilage. There was also a change from predominantly interterritorial to pericellular/territorial deposition of C OMP, This difference persisted until the age of 15 months, when the nontran sgenic controls also demonstrated articular cartilage degeneration and incr eased COMP immunostaining. Increased serum levels of COMP were seen in Del1 mice at the age of 4 months, correlating temporally with the onset of cart ilage degeneration. Conclusion. These findings suggest that up-regulation of COMP mRNA and redi stribution of the protein are characteristic of the early stages of articul ar cartilage degeneration in the transgenic mouse model in which OA results from a dominant-negative mutation in the type II collagen gene. The data p rovide additional support for the notion that COMP is a useful marker for a ltered cartilage metabolism in developing OA.