Abstract
Osteoarthritis (OA), a common degenerative joint disease, is principally characterized by inflammation and destruction of cartilage. Nobiletin, an extract of the peel of citrus fruits, is known to have anti-inflammatory properties. However, the mechanisms by which nobiletin plays a protective role in osteoarthritis (OA) are not completely understood. In the present study, we investigated the anti-inflammatory effects of nobiletin in the progression of OA in both in vitro and in vivo experiments. Mouse chondrocytes were pretreated with nobiletin (0, 10, 20, 40 μM) for 24 h and then incubated with IL-1β (10 ng/ml, 24 h) in vitro. The generation of PGE2 and NO was evaluated by the Griess reaction and ELISAs. The protein expression of inducible nitric oxide synthase, matrix metalloproteinase-3, matrix metalloproteinase-13, A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5), cyclooxygenase-2, collagen II, and aggrecan was analyzed by Western blotting. Immunofluorescence and Western blot analysis were used to detect nuclear factor-κB (NF-κB) signaling molecules. Induction of proinflammatory and catabolic mediators by IL-1β stimulation of mouse chondrocytes could be partially blocked by treatment with nobiletin or ammonium pyrrolidine dithiocarbamate (an NF-κB inhibitor). Furthermore, our results indicated that nobiletin exhibited a therapeutic effect through active inhibition of the NF-κB signaling pathway. In a mouse model of OA, injection of nobiletin (20 mg/kg) every 2 days for 8 weeks after surgery inhibited cartilage destruction and synovitis. Taken together, our findings suggest that nobiletin may be a potential therapeutic agent for the treatment of OA.
Highlights
Osteoarthritis (OA) is a common disease that often causes physical limitations, disability, and mental stress, in older people (French et al, 2015)
Primary antibodies directed against A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5), collagen II, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were purchased from Abcam (Cambridge, MA, USA), while primary antibodies against iNOS, MMP-3, matrix metalloproteinase-13 (MMP-13), cyclooxygenase-2 (COX-2), p-IkBα, IkBα, p-p65, and p65 were obtained from ProteinTech (Wuhan, China)
We investigated the expression of COX-2, INOS, MMP-3, MMP-13, and ADAMTS5 in IL-1β-stimulated cells by western blotting
Summary
Osteoarthritis (OA) is a common disease that often causes physical limitations, disability, and mental stress, in older people (French et al, 2015). There is no cure for osteoarthritis, as it is difficult to restore the cartilage. A large number of studies have demonstrated that trauma, obesity, inflammation, and age have a huge influence on the disease. It has been confirmed that a large number of inflammatory factors, such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), perform an important role in the progression of OA (Haq et al, 2010; Johnson and Hunter, 2014). Inhibition of the expression of IL-1β and IL-1β-induced inflammatory mediators may be a potential therapeutic route for attenuating the progression of OA. Researchers have investigated natural compounds as potential therapeutic agents for human diseases (Lu et al, 2015). Many anti-OA compounds have been widely used against OA, such as sanguinarine, resveratrol, and matrine
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