Emerging role of lncRNAs in osteoarthritis: An updated review.

Osteoarthritis (OA) is a prevalent joint disease, which is associated with progressive articular cartilage loss, synovial inflammation, subchondral sclerosis and meniscus injury. The molecular mechanism underlying OA pathogenesis is multifactorial. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs with length more than 200 nucleotides. They have various functions such as modulating transcription and protein activity, as well as forming endogenous small interfering RNAs (siRNAs) and microRNA (miRNA) sponges. Emerging evidence suggests that lncRNAs might be involved in the pathogenesis of OA which opens up a new avenue for the development of new biomarkers and therapeutic strategies. The purpose of this review is to summarize the current clinical and basic experiments related to lncRNAs and OA with a focus on the extensively studied H19, GAS5, MALAT1, XIST and HOTAIR. The potential translational value of these lncRNAs as therapeutic targets for OA is also discussed.

Wang R ，Shiu HT ，Lee WYW 《Frontiers in Immunology》

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis.

The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.

Chen WK ，Yu XH ，Yang W ，Wang C ，He WS ，Yan YG ，Zhang J ，Wang WJ ... -  《-》

The role and function of long non-coding RNAs in osteoarthritis.

Osteoarthiritis (OA) is the most prevalent disease of articulating joints in human that frequently results in joint pain, movement limitations, inflammation, and progressive degradation of articular cartilage. The etiology of OA is not completely clear and there is no full treatment for this disease. Molecular investigations have revealed the involvement of non-coding RNAs such as Long non-coding RNAs (lncRNAs) in OA pathogenesis. LncRNAs play roles in multiple cellular and biological processes. Moreover, numerous lncRNAs are differentially expressed in human OA cartilage. In this review, we underlie the increasing evidence for the critical role of lncRNAs in OA pathogenesis reviewing the latest researches.

Abbasifard M ，Kamiab Z ，Bagheri-Hosseinabadi Z ，Sadeghi I ... -  《-》

Identification of long noncoding RNA associated with osteoarthritis in humans.

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. 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. 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. 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.

Xing D ，Liang JQ ，Li Y ，Lu J ，Jia HB ，Xu LY ，Ma XL ... -  《-》

Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis.

To gain insight in the expression profile of long non-coding RNAs (lncRNAs) in OA subchondral bone. RNA sequencing data of macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N = 22 pairs; 5 hips, 17 knees, Research osteoArthrits Articular Tissue (RAAK study) was run through an in-house pipeline to detect expression of lncRNAs. Differential expression analysis between preserved and lesioned bone was performed. Spearman correlations were calculated between differentially expressed lncRNAs and differentially expressed mRNAs identified previously in the same samples. Primary osteogenic cells were transfected with locked nucleic acid (LNA) GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets. In total, 2816 lncRNAs were well-expressed in subchondral bone and we identified 233 lncRNAs exclusively expressed in knee and 307 lncRNAs exclusively in hip. Differential expression analysis, using all samples (N = 22 pairs; 5 hips, 17 knees), resulted in 21 differentially expressed lncRNAs [false discovery rate (FDR) < 0.05, fold change (FC) range 1.19-7.39], including long intergenic non-protein coding RNA (LINC) 1411 (LINC01411, FC = 7.39, FDR = 2.20 × 10-8), AC005165.1 (FC = 0.44, FDR = 2.37 × 10-6) and empty spiracles homeobox 2 opposite strand RNA (EMX2OS, FC = 0.41, FDR = 7.64 × 10-3). Among the differentially expressed lncRNAs, five were also differentially expressed in articular cartilage, including AC005165.1, showing similar direction of effect. Downregulation of AC005165.1 in primary osteogenic cells resulted in consistent downregulation of highly correlated frizzled related protein (FRZB). The current study identified a novel lncRNA, AC005165.1, being dysregulated in OA articular cartilage and subchondral bone. Downregulation of AC005165.1 caused a decreased expression of OA risk gene FRZB, an important member of the wnt pathway, suggesting that AC005165.1 could be an attractive potential therapeutic target with effects in articular cartilage and subchondral bone.

Tuerlings M ，van Hoolwerff M ，van Bokkum JM ，Suchiman HED ，Lakenberg N ，Broekhuis D ，Nelissen RGHH ，Ramos YFM ，Mei H ，Cats D ，Coutinho de Almeida R ，Meulenbelt I ... -  《-》