Expression profiles of long non-coding RNAs in the cartilage of patients with knee osteoarthritis and normal individuals

Abstract

Knee osteoarthritis is caused by a multifactorial imbalance in the synthesis and degradation of knee chondrocytes, subchondral bone and extracellular matrix. Abnormal expression of long non-coding RNAs (lncRNAs) affects the metabolism, synovitis, autophagy and apoptosis of chondrocytes, as well as the production of cartilage matrix. The aim of the present study was to identify novel targets for the treatment of osteoarthritis and to examine the pathogenesis of the disease. The lncRNA expression profiles of seven patients with knee osteoarthritis and six healthy controls were examined by RNA-sequencing. Differentially expressed lncRNAs were selected for bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Reverse transcription-quantitative PCR (RT-qPCR) was used to further investigate the differential expression of the lncRNAs. A total of 23,583 lncRNAs were identified in osteoarthritis cartilage, including 5,255 upregulated and 5,690 downregulated lncRNAs, compared with normal cartilage. Although there were more downregulated lncRNAs compared with upregulated lncRNAs, among the changed lncRNAs (fold-change >6), there were more upregulated lncRNAs compared with downregulated lncRNAs. Several lncRNAs exhibiting differences were identified as potential therapeutic targets in knee osteoarthritis. GO and KEGG pathway analyses were performed for the target genes of the differentially expressed lncRNAs. RT-qPCR validation was performed on three randomly selected upregulated and downregulated lncRNAs. The results of RT-qPCR were consistent with the findings obtained by RNA-sequencing analysis. The findings from the present study may contribute to the diagnosis of osteoarthritis and may predict the development of osteoarthritis. Furthermore, the differentially expressed lncRNAs may aid in the identification of novel candidate targets for the treatment of knee osteoarthritis.