Anti-inflammatory Effect of DNA polymeric Molecules in a Cell Model of Osteoarthritis

Abstract

The DNA polymeric molecules polydeoxynucleotide (PDRN) and polynucleotide (PN) can be used as new alternative treatment for osteoarthritis (OA); however, the underlying mechanisms are not fully understood. In this study, we investigated the effect of PDRN and PN on gene-expression profiles in a cell model of OA using transcriptome analysis. Under hypoxic conditions, human chondrosarcoma cells were stressed for 24 h in the presence of interleukin (IL)-1β and subsequently treated with PDRN, PN, or hyaluronic acid (HA) for another 24 h, followed by transcriptome analysis. The results of the transcriptome study comprising differentially expressed genes were analyzed using the Database of Annotation Visualization and Integrated Discovery program, which yielded Kyoto Encyclopedia of Genes and Genomes pathways. Toll-like receptor (TLR)- and nucleotide-binding oligomerization domain-like receptor (NLR)-signaling pathways were related between the IL-1β group and the group treated with DNA polymeric molecules. The genes involved in the TLR- and NLR-signaling pathways were validated using real-time quantitative polymerase chain reaction and western blot. Among these genes, IL-6, IL-1β, IL-8, and chemokine (C-C motif) ligand 3 were dramatically upregulated in the IL-1β group, but significantly downregulated in the group treated with DNA polymeric molecules. Specifically, PN treatment resulted in a greater decrease in the expression of these genes as compared with PDRN treatment. Both PDRN and PN treatments were involved in the anti-inflammatory response associated with OA progression, with PN treatment exhibiting additional anti-inflammatory properties relative to PDRN treatment. These results provide insight into potential therapeutic approaches involving PDRN and PN treatment of OA.