Identification of long noncoding RNA associated with osteoarthritis in humans

Objective: Long noncoding RNAs (lncRNAs) are an important class of genes involved in various biological functions; however, knowledge about lncRNAs in osteoarthritis (OA) is limited. Therefore, the present study aimed to identify which lncRNAs are expressed in OA versus normal cartilage.

Methods: To identify lncRNAs specifically expressed in OA cartilage, expression of lncRNAs in OA cartilage was compared with that in normal cartilage using microarray analysis. The identified differences in expression of lncRNAs were validated by real time polymerase chain reaction (RT-PCR). Furthermore, expression of several key mRNAs associated with OA, including those for matrix metalloproteinase (MMP)-9, MMP-13, bone morphogenetic protein (BMP)-2, COL2A1 and ADAMTS5, was investigated by RT-PCR in OA and normal cartilage.

Results: Microarray analysis identified 121 lncRNAs that were up- or down-regulated in OA compared with normal tissue, 73 being upregulated and 48 downregulated compared with normal cartilage. Twenty-one of the above differently expressed lncRNAs were up-regulated twofold. Expression of six lncRNAs, including HOTAIR, GAS5, PMS2L2, RP11-445H22.4, H19 and CTD-2574D22.4, was up-regulated in OA compared with normal tissue as validated by RT-PCR after microarray analysis. Expression of mRNA for MMP-9, MMP-13, BMP-2, and ADAMTS5 in OA was significantly greater than in normal cartilage. However, expression of mRNA for COL2A1 was lower in OA than in normal cartilage.

Conclusion: The differently expressed lncRNAs may be associated with the pathogenesis of OA. Further functional studies are critical to confirming the function of lncRNAs in OA and to exploring new potential targets for therapy.