The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis.

摘要: Clinically, osteoarthritis (OA) pain is significantly associated with synovial inflammation. Identification of the mechanisms driving inflammation could reveal new targets to relieve this prevalent state. Herein, a role polyadenylation in OA samples was investigated, and potential inhibitor cordycepin (3’ deoxyadenosine) inhibit as well reduce structural progression were studied. Joint tissues from people high or low grade non-arthritic post-mortem controls analysed for factor CPSF4 inflammatory markers. Effects on behavior joint pathology studied models (intra-articular injection monosodium iodoacetate rats surgical destabilisation medial meniscus mice). Human monocyte-derived macrophages mouse macrophage cell line used determine effects nuclear localisation transcription NFĸB factors (WDR33 CPSF4). NFκB expression increased synovia patients Cordycepin reduced behaviour, both models. Stimulation induced factors, inhibited by cordycepin. Knockdown also prevented NFĸB. The indicates target analgesia treatments. This supported finding that are required fact attenuates OA.