Objectives: Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods: Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results: Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions: Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA.

Inducible nitric oxide synthase (iNOS) is the key enzyme in NO synthesis and exhibits a high expression in numerous types of malignant tumors. Previous studies have demonstrated that iNOS promotes the production of tumor blood vessels by catalyzing the synthesis of additional NO. Certain experimental evidence has suggested that iNOS may regulate the levels of vascular endothelial growth factor (VEGF), as the level of VEGF may be induced by iNOS during endothelial cell migration and angiogenesis. In this study, it was observed that SiHa and HeLa cells exhibit depressed proliferation levels following the knockdown of iNOS with a lentivirus. In addition, NO levels demonstrated a correlation with VEGF levels in the cell culture supernatant.

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA, MALAT1) has been found to be aberrantly expressed in osteosarcoma, while high MALAT1 expression is correlated with both metastasis and prognosis. This meta-analysis set out to investigate the prognostic value of lncRNA MALAT1 in patients living with osteosarcoma. We conducted a systematical search of available databases from inception to May 2019. Odds ratios (OR) of clinical parameters, as well as hazard ratio (HR) of overall survival (OS), were calculated in order to evaluate the relationship between MALAT1 expression and the prognosis of patients living with osteosarcoma. Nine eligible studies which included a total of 599 osteosarcoma patients were enrolled in the present study. Pooled results found that high MALAT1 expression was associated with clinical stage and distant metastasis, but not age, gender, tumor anatomical location or tumor size. When compared to patients with low MALAT1 expression, patients with high MALAT1 expression were markedly correlated with a worse OS. Moreover, MALAT1 may be an independent predictive factor for OS in patients living with osteosarcoma. This meta-analysis suggests that high MALAT1 expression is associated with advanced clinicopathological features as well as unfavorable prognosis. LncRNA MALAT1 has the potential to serve as a moderate prognostic biomarker for osteosarcoma.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.