Long noncoding RNAs in osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis that may affect all joint tissues. Unfortunately, the pathogenesis of OA is not fully understood yet and it cannot be cured totally. Long noncoding RNA (lncRNA) is a type of RNA molecule greater than 200 nucleotides, and deregulated expression of lncRNAs plays an important role in many types of inflammation-related diseases. In this review, we have focused on the association of lncRNAs in the development and progression of OA and the possibility of lncRNAs as a therapeutic agent for the treatment of OA. Some lncRNAs are up-regulated in OA cartilage, and plays a critical role in the degradation of chondrocyte extracellular matrix, consequently weakening the integrity of the articular cartilage. Therapeutic targeting of these lncRNAs has shown significant influence on controlling OA progression. More clinical studies are in focus for OA treatment strategy by targeting lncRNAs.

Jiang SD ，Lu J ，Deng ZH ，Li YS ，Lei GH ... -  《-》

Long noncoding RNA TM1P3 is involved in osteoarthritis by mediating chondrocyte extracellular matrix degradation.

Osteoarthritis (OA) is a widespread degenerative joint disease characterized by articular cartilage degradation and is the leading cause of physical disability. Noncoding RNAs, especially long noncoding RNAs (lncRNAs) and microRNAs, are involved in the degradation of the chondrocyte extracellular matrix (ECM) in patients with OA. The present study was aimed to investigate the effects of lncRNA and miR-22 on the degradation of the chondrocyte ECM and underlying mechanisms. To simulate conditions found in OA, primary cultured chondrocytes were treated with IL-1, TGF-β, or sb525334. Real-time PCR and Western blot analysis were performed to detect expressions of miR-22, lncRNA-TM1P3, ALK1, MMP13, pSMAD1/5, SMAD1, and pSMAD5. Small interfering RNAs and a miR-22 mimic or inhibitor were utilized to determine lncRNA-TM1P3 knockdown and miR-22 overexpression or inhibition. The lncRNA-TM1P3 significantly upregulated in patients with OA, accompanied by the downregulation of miR-22 and upregulation of pSMAD1/5 and MMP13, which ultimately resulted in the degradation of the chondrocyte ECM in patients with OA. Bioinformatics analysis predicted miR-22 as a target of both lncRNA-TM1P3 and MMP13. The lncRNA-TM1P3 knockdown significantly increased the expression of ALK1, a corresponding increase in ECM degradation was observed by affecting the phosphorylation of SMAD1/5 and the expression of MMP13, which did not affect the expression of ALK1. These findings demonstrated that the lncRNA-TM1P3/miR-22/TGF-β signaling/MMP13 axis is involved in the degradation of chondrocyte ECM in patients with OA, which could provide novel therapies for OA treatment.

Li Y ，Li Z ，Li C ，Zeng Y ，Liu Y ... -  《-》

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 ... -  《-》

Roles of long non‑coding RNA in osteoarthritis (Review).

Wang J ，Sun Y ，Liu J ，Yang B ，Wang T ，Zhang Z ，Jiang X ，Guo Y ，Zhang Y ... -  《-》

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 ... -  《-》