Suppressive oligodeoxynucleotide-induced dendritic cells rein the aggravation of osteoarthritis in mice

Abstract

Objective: To explore the effect of suppressive oligodeoxynucleotide-induced dendritic cells (S-DCs) in the osteoarthritis (OA) therapy.Methods: S-DCs were prepared from splenic CD11c + cells by in vitro culture with suppressive oligodeoxynucleotide. The function and phenotypes of S-DCs were measured by ELISA and flow cytometry. The innate immune signaling pathways were detected by western blotting in the non-treated DCs and S-DCs upon stimulation. In vivo, we employed an iodoacetate-induced OA mice model. S-DCs were transferred by intravenous route. The weight bearing of mice was evaluated and pro-inflammatory factors in OA joint were measured by real-time PCR. Treg cell ratio and CD4 + IL10+ cells in spleen were detected by flow cytometry at day 5 post OA induction.Results: The S-DCs showed less inflammatory phenotypes upon stimulation. The expression of pro-inflammatory cytokines and mature makers in the S-DCs were blunt, due to the impaired innate immune signal transduction. In an iodoacetate-induced OA model, transfer of S-DCs significantly controlled the process of OA. Restricted inflammatory responses were observed in the joint of S-DC recipients. Moreover, after S-DC transfer, Tregs and CD4 + IL10+ cells were mounted in the spleen.Conclusion: Transfer of suppressive oligodeoxynucleotides-induced autologous DCs may represent a potential agent to control the aggravation of OA in patients.