The early molecular natural history of experimental osteoarthritis - I. Progressive discoordinate expression of aggrecan and type II procollagen messenger RNA in the articular cartilage of adult animals

Objective. To quantify changes in the chondrocyte metabolism of aggrecan co re protein and type II procollagen messenger RNA (mRNA) during the early an d middle phases of experimental osteoarthritis (OA) in animals. Methods. Experimental OA was induced by transecting the cranial cruciate li gament of the stifle joint in adult animals; articular cartilage was harves ted and analyzed after 4, 10, and 32 weeks. Results. Northern blot analysis revealed no change in aggrecan mRNA 4 weeks after surgery compared with aggrecan mRNA in the unoperated contralateral control joints; aggrecan mRNA levels became significantly elevated by 10 an d 32 weeks after surgery. In OA cartilage, type II procollagen mRNA was dra matically and progressively elevated at all times after surgery. The relati ve increases in type II procollagen mRNA exceeded the relative increases in aggrecan mRNA at all times after surgery, and these differences increased progressively over time, Articular chondrocytes became activated globally ( total RNA increases) and specifically (mRNA increase) early after joint inj ury and remained activated throughout the early and middle phases of this e xperimental OA. Conclusion, The early natural history of experimental OA is characterized b y a progressive imbalance in the mRNA expression of aggrecan and type IT pr ocollagen in articular chondrocytes. These results suggest that the stimuli for the transcription of these 2 genes are fundamentally different in this animal model.