NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

Objective: This study aimed to examine the temporal activation of NF-KB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA.Method: Following knee injury NF-kappa B activity was assessed longitudinally via in vivo imaging in FVB. CgTg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-kappa B signaling via intra-articular delivery of an I kappa B kinase two antagonist to understand how local NF-kappa B inhibition might alter disease progression. Results: Following joint injury NF-kappa B signaling within the knee joint was transiently increased and peaked on day 3 with an estimated 1.35 p/s/cm(2)/sr (95% CI 0.913.1.792 p/s/cm(2)/sr) fold increase in signaling when compared to control joints. Furthermore, injury resulted in the long-term development of hindpaw allodynia. Hyperalgesia withdrawal thresholds were reduced at injured knee joints, with the largest reduction occurring 2 days following injury (estimate of between group difference 129.1 g with 95% CI 60.9,197.4 g), static weight bearing on injured limbs was also reduced. Local delivery of an NF-kappa B inhibitor following joint injury reduced chondrocyte death and influenced the development of painrelated sensitivity but did not reduce long-term cartilage degeneration.Conclusion: These findings underscore the development of behavioral changes in this non-invasive loading model of PTOA and their relationships to NF-kappa B activation and pathology. They also highlight the potential chondroprotective effects of NF-kappa B inhibition shortly following joint injury despite limitations in preventing the long-term development of joint degeneration in this model of PTOA. (c) 2020 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.