Development of a Mouse Model of Knee Osteoarthritis Based on Obesity and Bipedal Walking.

To investigate the influence of obesity and obligatory bipedal walking on osteoarthritis (OA) development, 26-week-old C57BL/6 mice were divided into two groups and obesity was induced in one group with a 60% fat diet. After 8 weeks, mice from each group were again divided into two groups and obligatory bipedal exercise was induced with a specially designed treadmill in one group, resulting in four experimental groups (control, control bipedal, obese, and obese bipedal). After 8, 10, and 12 weeks of bipedal walking, knee joints were obtained and graded. Surface fibrillation and matrix proteoglycan depletion, began to appear after 8 weeks of exercise in the bipedal groups and progressed as the duration of the exercise increased. At 12 weeks, cartilage loss extending >75% of articular cartilage was observed in none of the control and obese groups, and in 42.8% and 77.7% of control bipedal and obese bipedal animals, respectively. OA grading was significantly higher in the obese bipedal group compared with the control bipedal group. The von Frey fiber test thresholds decreased significantly in the bipedal groups compared with the control and obese groups. This model can be used to study the pathogenesis of human OA and to evaluate its therapeutic agents. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2411-2419, 2019.

Phase 2 enzyme inducer sulphoraphane blocks prostaglandin and nitric oxide synthesis in human articular chondrocytes and inhibits cartilage matrix degradation.

OBJECTIVE: We explored the inhibitory effect of sulphoraphane (SFN), a potent inducer of Phase 2 enzymes, on cytokine-induced prostaglandin E(2) (PGE2) and nitric oxide (NO) production and cartilage degradation in articular chondrocytes. The regulatory mechanism of SFN on nuclear factor (NF)-κB was investigated. METHODS: Chondrocytes were obtained from patients with knee OA. Chondrocytes were stimulated with IL-1ß or TNF-α with or without pre-incubation with SFN. Production of PGE2 and NO was evaluated by the Griess reaction and an ELISA. The expression of microsomal PGE synthase (mPGES), cyclo-oxygenase (COX)-2 and inducible NO synthase (iNOS) was evaluated by real-time RT-PCR and western blot analysis. The regulation of NF-κB activity was explored using luciferase and chromatin immunoprecipitation assays as well as a western blot for phosphorylated IκB kinase (IKK), IκB and the degradation of IκB. Proteoglycan and type II collagen degradation products released from explant cultures were analysed using the dimethylmethylene blue assay and an ELISA for C-terminal telopeptides of type II collagen. RESULTS: SFN inhibited the production of PGE2 and NO induced by IL-1ß and TNF-α. At a concentration as low as 5 µM, SFN completely inhibited mPGES, COX-2 and iNOS at the mRNA and protein levels, and proteoglycan and type II collagen degradation product release in explant culture. Various signalling pathways required for the NF-κB activation were affected by SFN. CONCLUSION: SFN inhibited a broad range of catabolic mechanisms in articular chondrocytes. SFN may be a safe and effective candidate drug for the inhibition of cartilage degradation in arthritic diseases.