Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease, related to the overexpression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), inflammation, and chondrocyte apoptosis. Nesfatin-1 is an adipokine, which plays an important role in the development of OA, especially in obese people. In the present study, cartilage degradation and apoptosis observed in OA patients was evaluated. Furthermore, the anti-inflammatory and anti-apoptotic effects of nesfatin-1, and its underlying in vitro and in vivo mechanisms were investigated. The results showed that nesfatin-1 increased significantly the expression of collagen type II alpha 1 chain (Col2a1), and reduced the expression of MMPs, ADAMTS5, cyclooxygenase (COX)-2, caspase-3, nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), interleukin (IL)-6, and chondrocyte apoptosis rate, which may be induced by IL-1β in rat chondrocytes. Furthermore, nesfatin-1 treatment prevented cartilage degeneration in the rat OA model. It was found that nesfatin-1 suppressed the IL-1β-induced activation of NF-κB, the mitogen-activated protein kinase (MAPK), and the Bax/Bcl-2 signal pathway in chondrocytes. These results suggest that in vivo nesfatin-1 could play a protective role in the development of OA and can be potentially used for its treatment.
Highlights
Osteoarthritis (OA) is a common degenerative disease characterized by breakdown of the cartilage matrix, chondrocyte hypertrophy, inflammation of the synovial membrane, and osteophyte formation in the joints [1]
The apoptosis-related protein caspase-3, and the inflammatory-related marker COX-2 were significantly increased. These results indicated that cartilage degradation, apoptosis, and inflammation were evident in the OA samples as compared to the normal samples
On the other hand, compared to the cells treated with IL-1β, the cells treated with nesfatin-1 showed better viability. These results suggested that the IL-1β treatment reduced significantly the cell viability of chondrocytes, while nesfatin-1 exerted a protective effect on OA chondrocytes
Summary
Osteoarthritis (OA) is a common degenerative disease characterized by breakdown of the cartilage matrix, chondrocyte hypertrophy, inflammation of the synovial membrane, and osteophyte formation in the joints [1]. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are the established primary mediators of cartilage degradation in OA; whereas, apoptosis has www.aging-us.com been observed in OA cartilage, suggesting its role in the pathogenesis of the disease [6]. This apoptotic process has been found to be correlated with cartilage damage and hypocellularity [7]. Apoptosis has become a potential target for the treatment of OA and its understanding is essential for the design of new therapeutics [8, 9]
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