Long Non-coding RNA SNHG7 Suppresses Inflammation and Apoptosis of Chondrocytes Through Inactivating of p38 MAPK Signaling Pathway in Osteoarthritis.

This study aims to explore the molecular mechanism of LncRNA SNHG7 in Osteoarthritis (OA). Cartilage tissues of OA patients or patients with trauma or amputation were collected. Compared to normal cartilage tissues, SNHG7 was downregulated while miR-324-3p was upregulated in cartilage tissues of OA patients. IL-1β was used to induce damage to chondrocytes and treatment with IL-1β reduced SNHG7 expression in OA chondrocytes. In IL-1β-treated OA chondrocytes, SNHG7 overexpression reduced the levels of TNF-α and IL-6, inhibited cell apoptosis, and increased cell viability. Additionally, the luciferase reporter assay proved that SNHG7 upregulated dual-specificity phosphatase 1 (DUSP1) by sponging miR-324-3p, thereby inactivating the p38 MAPK signaling pathway by regulating the miR-324-3p/DUSP1 axis. Anisomycin (a p38 MAPK activator) enhanced OA chondrocytes inflammation, promoted cell apoptosis, and reduced cell viability; however, this was reversed by SNHG7 overexpression. This study demonstrates that the SNHG7/miR-324-3p/DUSP1 axis suppresses OA chondrocytes inflammation and apoptosis by inhibiting the p38 MAPK signaling pathway. Thus, this study indicates that SNHG7 is a novel target for OA treatment.

Sun H ，Li Z ，Liu N ，Xu T ，Hu K ，Shao Y ，Chen X ... -  《-》

LncRNA SNHG7 alleviates IL-1β-induced osteoarthritis by inhibiting miR-214-5p-mediated PPARGC1B signaling pathways.

Xu J ，Pei Y ，Lu J ，Liang X ，Li Y ，Wang J ，Zhang Y ... -  《-》

Knockdown of PVT1 inhibits IL-1β-induced injury in chondrocytes by regulating miR-27b-3p/TRAF3 axis.

Lu X ，Yu Y ，Yin F ，Yang C ，Li B ，Lin J ，Yu H ... -  《-》

Upregulation of long noncoding TNFSF10 contributes to osteoarthritis progression through the miR-376-3p/FGFR1 axis.

Osteoarthritis (OA) is a common joint disease with high morbidity, but there is still no definitive treatment for it. Long noncoding RNAs (lncRNAs) have been confirmed to play key roles in OA progression. This work was done to investigate the roles and action mechanism of lncRNA TNFSF10 in OA. The messenger RNA levels of TNFSF10 in articular cartilage samples from patients or chondrocytes were detected by Quantitative real-time PCR assay (qRT-PCR). The effects of TNFSF10 on chondrocytes were evaluated on the basis of cell growth, apoptosis, and inflammation. Then, the interaction between TNFSF10 and miR-376-3p was explored by dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay. Finally, various cell experiments, Western blot analysis, and qRT-PCR were performed to study the interaction among TNFSF10, miR-376-3p, and fibroblast growth factor receptor 1 (FGFR1). It was found that TNFSF10 was upregulated in OA cartilages and stimulated cell proliferation, antiapoptosis, and inflammation for chondrocytes. In addition, TNFSF10 acted as a competing endogenous RNA to downregulate miR-376-3p, and the influence of TNFSF10 on chondrocytes was partly reversed by miR-376-3p. Moreover, FGFR1, as a target of miR-376-3p, had reversal functions on the outcomes mediated by miR-376-3p. The further analysis displayed that there was a negative relationship between TNFSF10 and miR-376-3p as well as miR-376-3p and FGFR1, while FGFR1 was positively related with TNFSF10. Altogether, TNFSF10 overexpression probably stimulated proliferation and inflammation, and inhibited apoptosis by regulating the miR-376-3p/FGFR1 axis, implying that its increase contributed to OA progression. Our study provided a new potential biomarker or therapeutic target-TNFSF10, which was helpful to develop an efficient approach to cure OA.

Huang B ，Yu H ，Li Y ，Zhang W ，Liu X ... -  《-》

The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis.

Long-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms. Combined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins. Dual luciferase reporter gene and RIP to verify direct interaction of TUG1 with miR-144-3-p and miR-144-3-p with DUSP1, Annexin V-FITC/PI double staining to detect apoptosis. CCK-8 to detect cell proliferation. The biological significance of TUG1, miR-144-3p, and DUSP1 was assessed in vitro experiments using siRNA for TUG1, mimic and repressor for miR-144-3p, and overexpression plasmid for DUSP1. In this study, all data were subjected to a t-test or one-way analysis of variance with a p-value < 0.05 as the cutoff. TUG1 expression was closely associated with osteoarthritic chondrocyte damage, and knockdown of TUG1 significantly promoted chondrocyte apoptosis and inflammation. In the present study, we found that TUG1 inhibited chondrocyte apoptosis and inflammation by competitively binding miR-144-3p, deregulating the negative regulatory effect of miR-144-3p on DUSP1, promoting DUSP1 expression, and inhibiting the p38 MAPK signaling pathway. In conclusion, our study clarifies the role of the ceRNA regulatory network of TUG1/miR-144-3p/DUSP1/P38 MAPK in OA cartilage injury and provides an experimental and theoretical basis for genetic engineering tools to promote articular cartilage repair.

Liu NN ，Huang YP ，Shao YB ，Fan XF ，Sun HY ，Wang TR ，Yao T ，Chen XY ... -  《-》