Long non-coding RNAs (lncRNAs) have been proved to play important roles in the tumorigenesis and development of several human malignancies. Our study aims to investigate the expression and function of lncRNA-UCA1 in osteosarcoma. lncRNA-UCA1 expression was detected in osteosarcoma tissues and cell lines by using qRT-PCR. Association between lncRNA-UCA1 levels and clinicopathological factors and patient's prognosis was analyzed. The roles of lncRNA-UCA1 in regulating osteosarcoma cell proliferation, apoptosis, migration, and invasion were evaluated in vitro. We found that lncRNA-UCA1 expression was upregulated in osteosarcoma tissues and cell lines. High lncRNA-UCA1 expression was significantly correlated with large tumor size, high tumor grade, positive distant metastasis, and advanced clinical stage. Multivariate regression analysis identified lncRNA-UCA1 overexpression as an independent unfavorable prognostic factor. lncRNA-UCA1 knockdown inhibited osteosarcoma cell proliferation, promoted cell apoptosis, and suppressed cell invasion and migration, whereas lncRNA-UCA1 overexpression showed opposite effects. These findings suggested that lncRNA-UCA1 may contribute to osteosarcoma initiation and progression, and would be not only a novel prognostic marker but also a potential therapeutic target for this disease.

Adult human mesenchymal stem cells have the potential to differentiate into osteoblast, which plays crucial roles in bone regeneration and repair. Some transcriptional factors (TFs), such as BMP-2 and RUNX2, have been demonstrated to control the differentiation processes. It is important to discover more key regulators in osteoblast differentiation. Recently, some studies found long noncoding RNAs (lncRNAs) participating in osteoblast differentiation, such as MALAT1, DANCR, and ANCR. In this study, we performed a network-based computational analysis to investigate the lncRNA-messenger RNA (mRNA) crosstalks via integrating microRNA (miRNA)-RNA interactions, gene coexpression, and protein-protein interactions.First, multiple topology analyses were performed to osteoblast-differentiationrelated lncRNA-mRNA network (ODLMN). Several lncRNAs with central topology structures were identified as key regulators. Results showed that these lncRNAs participated in osteoblast differentiation via phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase, and Ras signals. Previous studies have demonstrated that lncRNAs exert functions by involving in close modules. Second, after performing module searching in ODLMN, two functional modules were identified, which played crucial roles through involving in PI3K/protein kinase B, cyclic adenosine 3ʹ,5ʹ-monophosphate, and hypoxia-inducible factor 1 pathways. Third, a subset of core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in osteoblast differentiation was identified. These core lncRNA-TF feedback loops showed more TF binding affinity than other lncRNAs.All these results can help us to uncover the molecular mechanism and provide new targets for bone regeneration and repair.

To date, a safe and reliable treatment of osteoarthritis (OA) has not yet been announced. Inflammatory response and degradation of the articular extracellular matrix (ECM) induced by IL-1β are important pathological characteristics of OA. Laquinimod is a quinoline-3-carboxamide and a novel oral immunomodulatory compound in clinical use. However, whether laquinimod has a beneficial effect in OA is not known. In our research, we found that laquinimod could ameliorate IL-1β-induced generation of ROS and improve mitochondrial function by increasing mitochondrial membrane potential (ΔΨm). Furthermore, treatment with laquinimod suppressed IL-1β-induced production of TNF-α and IL-6. Notably, laquinimod prevented the degradation of type II collagen by inhibiting MMP-3 and MMP-13. Meanwhile, the presence of laquinimod attenuated the reduction in aggrecan by mediating ADAMTS-4 and ADAMTS-5. Mechanistically, laquinimod ameliorated IL-1β-induced inflammation and degeneration of ECM by suppressing the activation of NF-κB. Taken together, our findings reveal that laquinimod possesses a beneficial effect against IL-1β insults in human chondrocytes, implying an important role of laquinimod in OA.

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