TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN CANINE OSTEOARTHRITIS - IMMUNOLOCALIZATION OF TNF-ALPHA, STROMELYSIN AND TNF RECEPTORS IN CANINEOSTEOARTHRITIC CARTILAGE

The presence and distribution of tumor necrosis factor-alpha (TNF-alph a), TNF receptors and stromelysin [matrix metalloproteinase 3 (MMP-3)] in articular cartilage were evaluated in an iatrogenically induced mo del of osteoarthritis (OA). Eleven adult male dogs were assigned rando mly to a control group (N=4) or an OA group (N=7). Osteoarthritis was created by surgical transection of the cranial cruciate ligament of on e stifle joint. Both femoral condyles were sampled 3 months post-surge ry at necropsy and immunohistochemically analyzed for the presence of the aforementioned cytokines and receptors. Chondrocytes stained for T NF-alpha and TNF receptors in control articular cartilage, spanning an area encompassing most of the middle and deep zones. Positive matrica l and chondrocytic staining for TNF-alpha, TNF receptors, and stromely sin was present in OA articular cartilage. Staining varied in intensit y and distribution and was dependent on the severity of the lesion. Sm ooth muscle cells of arteries and arterioles (periarticular synovial m embrane) were stained for only one (p55) of two TNF receptors; this st aining was confined to control tissues. Results indicate that the diff erential expression of TNF-alpha and its receptors may be important in the normal maintenance of articular cartilage. The increased presence of TNF-alpha and its receptors in articular cartilage with mild osteo arthritic changes suggests a role in the development of early OA. Regu lating TNF-alpha may be an important component in the treatment of OA.