Fig. 5.

CST protects against OA development by interacting with the TNF/TNFR signaling pathway. (A, B) Therapeutic effect of CST in TNFR1−/− and TNFR2−/− mice was abolished in TNFR1/2−/− mice, with the detection of Safranin-O staining and OARSI scoring. (C—F) CST delivery diminished expression levels of ADAMTS-5, MMP-13, IL-1β and iNOS in TNFR1−/− and TNFR2−/− mice but showed no difference in TNFR1/2−/− mice as detected through a Real-time PCR assay. (G) ADAMTS-5, MMP-13 and iNOS were diminished with CST treatment in TNFR1−/− and TNFR2−/− mice but not in TNFR1/2−/− mice as determined through immunohistochemistry (of DMM models, at the time of 8 week). (H) ELISA for IL-1β showed the protective effects of CST, but these effects were greatly diminished in TNFR1/2−/− mice. (I-J) Detection of iNOS showed that the levels were all alleviated with CST treatment in TNFR1−/− and TNFR2−/− mice but not in TNFR1/2−/− mice, as assayed by western blotting (*p < .01 vs control group). n = 7 for each group, Scale bar: 50 μm.