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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
Highlights
Osteoarthritis (OA), which is characterized by alteration in the architecture and composition of joints has adverse impact on socio-economic development [1, 2]
Administration of benzoxime to OA rats reversed the effects produced by monosodium iodoacetate (MIA) (Figure 1A)
Studies have demonstrated that the expressions of interleukin4, tumor necrosis factor-α, interleukin-6, and interleukin-13 are promoted by P2X7 receptor (P2X7R) activation [17]
Summary
Osteoarthritis (OA), which is characterized by alteration in the architecture and composition of joints has adverse impact on socio-economic development [1, 2]. Purinergic membrane receptor P2X expression in cartilage tissues has been shown to be associated with the onset of pain in OA patients [10]. The present study was undertaken to investigate the effect of benzoxime on cartilage tissue degradation in OA rats and the mechanism involved. The rats in the treatment group were intraarticularly injected 5 mg/kg benzoxime daily for 21 days. Following benzoxime treatment for 21 days, the OA rats were examined for asymmetry in bearing weight for the hind limb, and their paw withdrawal thresholds were evaluated. The difference between the two hind limbs was used to determine paw withdrawal threshold. Sliced cartilage tissues from the treatment, OA and vehicle groups of rats were subjected to homogenization in TRIzol® (50mg fresh weight/mL; Invitrogen, Paisley, UK) in liquid nitrogen using a dismembrator (Sartorious, Epsom, UK). Differences were considered statistically significant at p < 0.05
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