Background: A group of differentially expressed long non-coding RNAs (lncRNAs) have been shown to play key roles in osteoarthritis (OA), although they represented only a small proportion of lncRNAs that may be biologically and physiologically relevant. Since our knowledge of regulatory functions of non-coding RNAs is still limited, it is important to gain better understanding of their relation to the pathogenesis of OA.
Methods: We performed mRNA and lncRNA microarray analysis to detect differentially expressed RNAs in chondrocytes from three OA patients compared with four healthy controls. Then, enrichment analysis of the differentially expressed mRNAs was carried out to define disease molecular networks, pathways and gene ontology (GO) function. Furthermore, target gene prediction based on the co-expression network was performed to reveal the potential relationships between lncRNAs and mRNAs, contributing an exploration of a role of lncRNAs in OA mechanism. Quantitative RT-PCR analyses were used to demonstrate the reliability of the experimental results.
Findings: Altogether 990 lncRNAs (666 up-regulated and 324 down-regulated) and 546 mRNAs (419 up-regulated and 127 down-regulated) were differentially expressed in OA samples compared with the normal ones. The enrichment analysis revealed a set of genes involved in cell cycle. In total, 854 pairs of mRNA and lncRNA were highly linked, and further target prediction appointed 12 genes specifically for their corresponding lncRNAs. The lncRNAs lncRNA-CTD-2184D3.4, ENST00000564198.1, and ENST00000520562.1 were predicted to regulate SPC24, GALM, and ZNF345 mRNA expressions in OA.
Interpretation: This study uncovered several novel genes potentially important in pathogenesis of OA, and forecast the potential function of lnc-CTD-2184D3.4, especially for the cell cycle in the chondrocytes. These findings may promote additional aspects in studies of OA.