Osteoarthritis (OA) is a musculoskeletal degenerative joint disorder and a leading cause of pain and disability(1). In attempting to identify drug targets for the development of therapeutics that can prevent the progression of early OA preclinical models are critical. Currently, rodent preclinical models are used for this purpose. However, OA joint damage in these models is predominantly induced through chemical or surgical means, poorly reflecting human OA. Furthermore, these models provide limited tissue for ex vivo studies. Therefore, in this study we assessed whether the commercial pig might present an alternative model of early OA. To this end, we examined whether cartilage joint degeneration occurred spontaneously in female pigs (chondropathy scoring; 2), and determined the effect of the cytokines IL-1β, leptin, resistin and visfatin (3) on mediating the production of IL-6 (ELISA) and proteoglycan loss on porcine cartilage explant tissue (DMMB sGAG assay). All values represent means ± S.E.M (n=6), compared by one-way ANOVA. Chondropathy scoring carried out using the Collin’s grading and revised Systeme Francaise D’Arthroscopie (SFA) scoring systems was used to establish the severity of joint damage. Pigs as young as 17 wks show some signs of spontaneous osteoarthritis (Collin’s grade: 2.167 ± 0.3073, Revised SFA: 20.15 ± 4.004, n=6), with lesions developing on both the medial and lateral articular surfaces of the knee joint. Stimulation of porcine cartilage explant for 24 h with recombinant porcine IL-1β (0.1, 0.3, 1, 3 or 10 ng/ml) significantly induced proteoglycan degradation (Control: 238.9±37.16 p=0.0096, 0.1ng/ml: 380.6±33.64 p< 0.0001, 0.3ng/ml: 538.3±34.91 p< 0.0001, 1ng/ml: 597.2±31.97 p< 0.0001, 3ng/ml: 626.2±22.99 p< 0.0001, 10ng/ml: 693.8±25.54 p< 0.0001) and IL-6 secretion (Control: 118.1±57.61, 0.1ng/nl: 9068±1563 p=0.7475, 0.3ng/ml: 22020±2922 p= 0.0475, 1ng/ml: 46276±7588 p< 0.00013ng/ml: 92503±7658 p< 0.0001 10ng/ml: 73229±8650 p< 0.0001). Similarly, stimulation of porcine cartilage for 24 h with recombinant human visfatin (500ng/ml) induced significant proteoglycan degradation (Control: 238.9 ± 37.16, Visfatin: 366.0 ± 46.05, p= 0.0426) and IL-6 secretion (Control: 1296 ± 528.5, Visfatin: 20876 ± 4157, p< 0.0001). In both cases, the induction was similar to that observed with human OA cartilage explant tissue. In contrast, we observed no significant effect of either leptin (100 or 300ng/ml) or resistin (30 or 100ng/ml) on either proteoglycan degradation or IL-6 secretion. In summary, commercial pigs spontaneously develop signs of OA-like cartilage lesions by the age of 17 weeks. Furthermore, stimulation of porcine cartilage explants with either IL-1β or visfatin promotes proteoglycan degradation and IL-6 secretion, similar to that observed in human OA cartilage obtained from joint replacement procedures.