Tumor Necrosis Factor-alpha (TNF-alpha) in Canine Osteoarthritis: Immunolocalization of TNF-alpha, Stromelysin and TNF Receptors in Canine Osteoarthritic Cartilage

The presence and distribution of tumor necrosis factor-alpha (TNF-alpha), TNF receptors and stromelysin [matrix metalloproteinase 3 (MMP-3)] in articular cartilage were evaluated in an iatrogenically induced model of osteoarthritis (OA). Eleven adult male dogs were assigned randomly to a control group (N = 4) or an OA group (N = 7). Osteoarthritis was created by surgical transection of the cranial cruciate ligament of one stifle joint. Both femoral condyles were sampled 3 months post-surgery at necropsy and immunohistochemically analyzed for the presence of the aforementioned cytokines and receptors. Chondrocytes stained for TNF-alpha and TNF receptors in control articular cartilage, spanning an area encompassing most of the middle and deep zones. Positive matrical and chondrocytic staining for TNF-alpha, TNF receptors, and stromelysin was present in OA articular cartilage. Staining varied in intensity and distribution and was dependent of the severity of the lesion. Smooth muscle cells of arteries and arterioles (periarticular synovial membrane) were stained for only one (p55) of two TNF receptors; this staining was confined to control tissues. Results indicate that the differential 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 osteoarthritic changes suggests a role in the development of early OA. Regulating TNF-alpha may be an important component in the treatment of OA.