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Wnt inhibitory factor (WIF)-1 is a potent extracellular Wnt antagonist which may be used as a potential molecular therapy for the treatment of inflammatory and autoimmune diseases. Although previous studies have demonstrated that WIF-1 has a protective role in experimental studies of arthritis, its role in the various disease grades of osteoarthritis (OA) remains unclear. A total of 40 patients with various stages of primary OA of the knee and 10 control subjects were enrolled in the present study. Articular cartilage specimens were harvested from subjects following total knee arthroplasty or knee above amputation. Disease severity was determined according to Modified Mankin score and cartilage tissues were ascribed to four groups: Normal, mild, moderate and severe lesions. WIF-1 expression levels in articular cartilage were measured using immunohistochemical techniques. WIF-1 expression levels were detected in all cartilage tissues. As compared with the controls, patients with OA exhibited significantly decreased WIF-1 expression levels in the articular cartilage (0.19±0.05 vs. 0.26±0.04; P<0.01). Furthermore, articular cartilage WIF-1 expression levels in the moderate and severe lesion groups were significantly reduced, as compared with the controls (P<0.01) and mild lesion group (P<0.05). Subsequent analysis demonstrated that articular cartilage WIF-1 expression levels were negatively correlated with the severity of disease (r=-0.896, P<0.001). In conclusion, the results of the present study suggested that WIF-1 expression levels in articular cartilage may be negatively associated with progressive joint damage in patients with OA of the knee; therefore, WIF-1 expression may be a potential indictor for monitoring OA disease severity. [ABSTRACT FROM AUTHOR]