IL-1beta induction of the unfolded protein response (UPR) mediators XBP1s and chop drives pro-catabolic responses of human articular chondrocytes

Abstract

paws in the CCI group, compared to sham, on all days after day 3 (Fig. 1B).; thermal sensitivity similarly increased (p<0.05) in the ipsilateral paws of the CCI group as compared to sham. Both mechanical allodynia and thermal hyperalgesia were strongly correlated to NF-kB activity with Spearman r coefficients of -0.83 (p<0.0001) and -0.80 (p<0.0001), respectively (Fig. 1C). Multiple linear regression analysis demonstrated that in vivo NF-kB activity in the ROI (Fig 1A) was best described by sciatic nerve and adjacent muscle NF-kB activity (R21⁄4.79, p<0.0001). Both the muscle (p<0.001) and sciatic nerve (p<0.002) NF-kB activity were significant explanatory variables on day 3, but only the sciatic nerve (p<0.001) was significant on day 28. Conclusions: This study demonstrates the use of non-invasive luminescence in vivo imaging to measure NF-lB activity in a mouse model of radiculopathy and the correspondence of a key molecular event in nerve injury to pain sensitivity development. Increased NFkB activity at the ipsilateral ROI in the CCI model was strongly correlated to developing pain sensitivities. The demonstrated relationship between NFlB activity, mechanical allodynia, and thermal hyperalgesia suggests the use of NFlB luminescence imaging as a novel imaging biomarker of pain sensitivities and neuropathy in this model of radiculopathy. Acknowledgments: NIH AR047442, NIH AR050245.