Runx3 alleviates osteoarthritis through microRNA regulating multiple inflammation-related pathways

Objective Runt-related transcription factor 3 (Runx3), a transcript factor, plays an important role in accelerating chondrocyte differentiation and maturation. However, the role of Runx3 in regulating osteoarthritis (OA) is still unclear. Design: IL-1β was used to establish a cellular OA model in primary chondrocytes. The proliferation and differentiation of chondrocytes was detected by Alcian blue staining, qRT-PCR and flow cytometry. RNA-seq was performed to analyze the microRNA (miRNA) expression profiles in chondrocytes that over-expressed (OE) or silenced (SI) Runx3. Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Targetscan analyses were used to assess the function of identified differentially expressed miRNAs (DEMs) and their targets. Results It was found that Runx3 was highly expressed in OA patients. Silencing of Runx3 has the potential to improve the expression of Acan inhibit MMP13 and arrest cell cycle in the S phase in the OA chondrocytes. Based on the RNA-seq data, a total of 208 DEMs in SI vs blank group, and 187 DEMs in OE vs blank group were identified. KEGG analysis showed that Runx3 mainly affected inflammation-related signaling pathways including TNF-signaling pathway, NF-κB signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, et al. Conclusions Silencing of Runx3 has the ability to relieve OA development, and then revealed key miRNAs and pathways regulated by Runx3, thus not only offering new insight into the mechanisms regulatory by Runx3, but also providing potential candidates for repairing cartilage damage or OA.