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Published:
May 9, 2018DOI:
10.4314/tjpr.v17i3.8Keywords:
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Main Article Content
Benzoxime inhibits matrix metalloproteinase-13 activation and cartilage damage in osteoarthritis rats via inhibition of NF-κB pathway
Abstract
Purpose: To investigate the effect of benzoxime on degradation of articular cartilage in a rat model of osteoarthritis (OA), and the mechanism involved.
Methods: The OA rat model was prepared by injecting monosodium iodoacetate (MIA) intra-articularly to Wistar rats. Rats in the treatment group were given benzoxime (5 mg/kg) daily for 21 days through the intra-articular route. The animals were then examined for behavioral changes by assessment of asymmetry in bearing weight and paw withdrawal threshold of the hind limb. Western blot assay was used for the analysis of inflammatory cytokine expressions.
Results: The expression of P2X purinoceptor 7 receptor (P2X7R) mRNA was significantly elevated in the OA rats (p < 0.02). However, benzoxime treatment caused a marked decrease in the level of P2X1-8R mRNA. Benzoxime treatment also prevented asymmetry in bearing weight, decreased paw withdrawal threshold, and inhibited the expressions of interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and cartilage. Moreover, benzoxime exhibited significant inhibitory effects on the expressions of P2X7R, matrix metalloproteinase (MMP)-13 and prostaglandin E2 (PGE2) in cartilage tissue. It also significantly suppressed OA-induced increases in the levels of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, IκBα and NF-κB p65, and blocked OA-induced increases in the expressions of P2X7R, MMP-13 and PGE2.
Conclusion: These results demonstrate that benzoxime prevents cartilage degradation in OA rats by targeting NF-κB signaling pathway. Thus, benzoxime possesses clinical and therapeutic potentials for the prevention of cartilage degradation in OA.
Keywords: Interleukin-1β, Purinoceptor-7, Benzoxime, Osteoarthritis, Prostaglandin, Matrix metalloproteinases
