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.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cpr.12313

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis

Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis. The expression of miR-17-5p was down-regulated, while alpha-1, 2 fucosyltransferase 2 (FUT2) was increased in OA progression. Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that HOTAIR could directly bind to miR-17-5p and indirectly upregulate FUT2 level. Functional investigation revealed HOTAIR and FUT2 aggravated ECM degradation and chondrocytes apoptosis, and this effect could be reversed by miR-17-5p. Altered FUT2 modulated the activity of wnt/β-catenin pathway and HOTAIR/miR-17-5p also mediated wnt/β-catenin pathway through FUT2. Collectively, our findings indicated that HOTAIR/miR-17-5p/FUT2 axis contributed to OA progression via wnt/β-catenin pathway, which might provide novel insights into the function of lncRNA-driven in OA.

/pdf/long-non-coding-rna-hotair-promotes-osteoarthritis-wjj1c2f6b5.pdf

Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis

Osteoarthritis (OA) is a chronic joint disease and there is no a definitive cure at present. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in the development of OA. However, the underlying mechanism of lncRNA maternally expressed gene 3 (MEG3) in OA has not been well elucidated. The rat OA model and interleukin-1β (IL-1β)-induced rat chondrocytes were constructed. The expression pattern of lncRNA MEG3 and miR-16 was detected by RT-qPCR assay in cartilage tissues of rat OA model. The effect of MEG3 and miR-16 on IL-1β-induced chondrocytes was evaluated on the basis of cell viability and apoptosis. Then, the interaction among MEG3, miR-16 SMAD7 was explored by dual-luciferase reporter assay and RIP assay. It is found that lncRNA MEG3 was down-regulated and miR-16 was up-regulated in rat OA cartilage tissues. MEG3 knockdown promoted proliferation and inhibited apoptosis, while miR-16 knockdown suppressed proliferation and promoted apoptosis in IL-1β-induced rat chondrocytes. Moreover, MEG3 was involved in miR-16 pathway and MEG3 suppressed miR-16 expression. Additionally, SMAD7 was a target gene of miR-16 and miR-16 suppressed SMAD7 expression in IL-1β-induced chondrocytes. Moreover, the expression of SMAD7 induced by MEG3 or si-MEG3 was markedly reversed by the introduction of miR-16 or anti-miR-16. Furthermore, MEG3 exerted its anti-proliferation and pro-apoptosis by regulating miR-16 and SMAD7. MEG3 was down-regulated and miR-16 was up-regulated in cartilage tissues of rat OA model. MEG3 knockdown might lead to the progression of OA through miR-16/SMAD7 axis.

/pdf/the-lncrna-meg3-downregulation-leads-to-osteoarthritis-2cwh4iwl3n.pdf

The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis

The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA. Participants were divided into three groups. The control  group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman’s correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA. First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively. Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA.

Peng Wang

Papers

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