The emerging role of lncRNAs in chondrocytes from osteoarthritis patients.

Long non-coding RNAs (lncRNAs) play important roles in many physiological and pathological processes, including osteoarthritis (OA). Recent studies have demonstrated that lncRNAs are involved in the pathogenesis of OA by affecting various essential cellular features of chondrocytes, such as proliferation, apoptosis, inflammation, and degradation of the extracellular matrix (ECM). However, there are only a limited number of studies in this area, indicating that the role of lncRNAs in OA may have been overlooked. The aim of this literature review is to summarize the versatile roles and molecular mechanisms of lncRNAs in chondrocytes involved in OA. At the end of this article, the function of the lncRNA HOX transcript antisense RNA (HOTAIR) in chondrocytes in OA is highlighted. Because lncRNAs affect proliferation, apoptosis, inflammatory responses, and ECM degradation by chondrocytes in OA, they may serve as potential biomarkers or therapeutic targets for the diagnosis or treatment of OA. The specific role and related mechanisms of lncRNAs in OA warrants further investigation.

Tu J ，Huang W ，Zhang W ，Mei J ，Zhu C ... -  《-》

Long-chain non-coding RNA HOTAIR promotes the progression of osteoarthritis via sponging miR-20b/PTEN axis.

Cumulative evidence suggests that long-chain non-coding RNA (lncRNA) is involved in the pathogenesis of osteoarthritis (OA). The present study aimed to explore the regulatory role and related mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in OA. The OA mouse model was constructed by the medial meniscus (DMM) method, and Interleukin (IL)-1β-induced chondrocytes were used to simulate OA in vitro. Results found that HOTAIR was significantly up-regulated in articular cartilage tissues of OA mice and IL-1β-induced chondrocytes, accompanied by down-regulation of miR-20b and increased expression of the phosphatase and tensin homolog (PTEN). HOTAIR silencing improved cartilage tissue damage in OA mice, and promoted the expression of collagen II and aggrecan in cartilage tissue, while inhibited the expression of matrix metalloproteinases (MMP)-13 and ADAMTS-5. Overexpression of HOTAIR inhibited the proliferation of IL-1β-induced chondrocytes and promoted apoptosis and extracellular matrix (ECM) degradation, whereas the effect of HOTAIR knockdown was reversed. Bioinformatics software and luciferase reporter experiments confirmed that HOTAIR could negatively regulate miR-20b, and PTEN was a target gene of miR-20b. An increase in PTEN expression induced by HOTAIR overexpression could be reversed by the introduction of miR-20b mimic. HOTAIR overexpression significantly reversed miR-20 mimic-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes, whereas the introduction of si-HOTAIR eliminated anti-miR-20b-mediated apoptosis and ECM degradation. HOTAIR can participate in OA by promoting chondrocyte apoptosis and ECM degradation, which may be related to its targeted regulation of miR-20b/PTEN axis.

Chen Y ，Zhang L ，Li E ，Zhang G ，Hou Y ，Yuan W ，Qu W ，Ding L ... -  《-》

LncRNA PART1 modulates chondrocyte proliferation, apoptosis, and extracellular matrix degradation in osteoarthritis via regulating miR-373-3p/SOX4 axis.

Zhu YJ ，Jiang DM 《-》

Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis.

Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA. To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses. Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1β and tumor necrosis factor α. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix-degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR. The results indicate that lncRNA-CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA-CIR could be used as a potential target in OA therapy.

Liu Q ，Zhang X ，Dai L ，Hu X ，Zhu J ，Li L ，Zhou C ，Ao Y ... -  《-》

Upregulation of lncRNA HOTAIR contributes to IL-1β-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is a common and heterogeneous disease that causes painful and progressive joint degeneration, which restricts daily activities, including talking and chewing. Long noncoding RNAs (lncRNAs) are an important class of genes involved in various physiological and pathological functions, including osteoarthritis (OA).The present study aimed to identify the lncRNAs that are important in TMJ OA and their potential functions. Here, we found that HOTAIR was significantly upregulated in the synovial fluid of TMJ OA patients compared with that of normal controls. Increased HOTAIR was similarly observed in the synovial fluid of TMJ OA rabbits as compared to control rabbits. Furthermore, in interleukin-1β (IL-1β)-induced TMJ OA in vitro model (primary rabbit condylar chondrocytes), the expressions of matrix metalloproteinase (MMP)-1, MMP3, MMP9 and HOTAIR were all dramatically increased. Most importantly, knockdown of HOTAIR in IL-1β-induced TMJ OA in vitro model could not only reverse the IL-1β-stimulated expressions of MMP1, MMP3 and MMP9, but also significantly decrease the apoptosis rate induced by IL-1β in primary rabbit condylar chondrocytes. Our data provides new insight into the mechanisms of chondrocytes destruction in TMJ OA.

Zhang C ，Wang P ，Jiang P ，Lv Y ，Dong C ，Dai X ，Tan L ，Wang Z ... -  《-》