EFECTO DEL FACTOR DE TRANSFERENCIA SOBRE EL PERFIL PROINFLAMATORIO Y ANTIINFLAMATORIO DEL CARTILAGO ARTICULAR EN OSTEOARTRITIS INDUCIDA EN RATA

Abstract

Osteoarthritis (OA) is a progressive, degenerative joint disease characterized by irreversible loss of cartilage with subchondral area remodeling and inflammation of the synovial membrane. OA is the arthropathy considered the most common in people over 65 years old and is clinically characterized by stiffness and joint pain, limited mobility and local inflammation. Current treatments only modulate pain and reduce inflammation. However, there is no treatment to regenerate articular damaged. The pathophysiology of the disease involves the participation of various pro- and anti-inflammatory cytokines, which have been proposed as therapeutic targets through the use of immunotherapies to regulate the anabolic and catabolic pathways. The use os transfer factor (TF) in patients with OA, have showed regression of symptoms and modulation pain. However, there is no molecular studies that describe its mechanism of action. Therefore in this study we evaluate histologically the effect of FT in the development and progression of murine OA and its relationship to pro-inflammatory and anti-inflammatory articular cartilage profile. We used wistar rats, to induced OA by unilateral medial meniscectomy and high impact exercise for 20 days. The animals were killed, femoral condyle and tibial plateau of the affected joint was obtein to performed histopathological studies, expression analisis of pro-and anti-inflammatory and immunolocalization of both in the articular cartilage. The results showed that cartilage explants obtained from animals with OA treated with TF did not show changes in the distribution and the cellular architecture; there was no cellular dysplasia, or clustering of chondrocytes in clones. On the other hand a reduced degradation of extracellular matrix components (collagen and proteoglycans) was evidented showing histological features more similar to normal articular cartilage. The expression of anti-inflammatory cytokines by RT-PCR, showed that the cartilage of animals with OA without treatment, no expression of FGF-2 and IFN γ was detected showing only low expression of PDGF. However, in animals treated with TF the expression of anti-inflammatory cytokines PDGF, IFNγ, FGF-2 significantly increased compared to that observed in healthy cartilage. That analysis of pro-inflammatory cytokines expression in FT treated animals did not displayed the expression of IL-1, however, we note that the expression of IκB was lower than compared with samples from animals without treatment. The localitation and expression of inmunohistofluorescence FGF-2 and PDGF in tissue, were found in normal cartilage and cartilage from OA animals treated with TF OA, correlating with the findings of the RT-PCR. Also similar weakly expression of unphosphorylated IκB was also observed in healthy and OA TF treated their animals. The results present here allows us to suggest that FT promotes a mechanism of action by increasing the expression of anti-inflammatory cytokines and reduction of some pro-inflammatory cytokines, thereby balancing the loss OA chondrocyte homeostasis for regulation of anabolic and catabolic processes of the ECM.