Application of Formononetin for the Treatment of Knee Osteoarthritis Induced by Medial Meniscectomy in a Rodent Model

Abstract

Formononetin suppresses catabolic effects in primary rat chondrocytes induced by IL-1β, which makes it a promising candidate for in vivo studies on the treatment and prevention of osteoarthritis (OA). The goal of this study is to investigate the effects of the oral administration of formononetin in a rodent model of OA. OA was induced by medial meniscectomy in the right knee joint of rats. The animals were assigned into four groups (n = 6): Vehicle (treated with saline), FNT10 (formononetin, 10 mg/kg), Ibuprofen (10 mg/kg), and Sham (simulated surgery, treated with saline). The treatment of the animals was performed daily by the oral route. After six weeks, the knee joints were removed and histologically processed. Histological sections stained in Safranin-O were used to assess the histological grading of the articular cartilage damage. An analysis of the immunohistochemical expression of type II collagen and IL-1β was also performed. The oral administration of formononetin significantly reduced cartilage-matrix-loss width (p < 0.01), degeneration scores (p < 0.05), and the total articular cartilage-wear depth (p < 0.01) in comparison with Group Vehicle. Type II collagen immunoexpression was intense and homogeneous in FNT10, comparable to that of Sham, scarce and irregularly distributed in Vehicle, and homogeneous but less intense in Ibuprofen. Furthermore, formononetin significantly reduced the immunohistochemical expression of IL-1β in joint chondrocytes (p < 0.01), but ibuprofen did not (p > 0.05). From this study, the oral administration of formononetin was found to attenuate OA-associated pathological damage in rodents, likely because of IL-1β expression downregulation in chondrocytes. These findings suggest that formononetin is a potential therapeutic for treatment.