CircRNA hsa_circ_0005105 upregulates NAMPT expression and promotes chondrocyte extracellular matrix degradation by sponging miR-26a.

Osteoarthritis (OA) is a chronic disease pathologically characterized by articular cartilage degeneration and damage. Currently, studies have found that circular RNA (circRNA) is involved in intracellular RNA regulating network and is closely related to the occurrence and development of diseases, therefore it may become a new biological marker and therapeutic target. After stimulating chondrocytes with interleukin-1 beta (IL-1β), hsa_circ_0005105 expression was significantly upregulated, while miR-26a expression was significantly inhibited. Hsa_circ_0005105 did not influence miR-26a expression but inhibited its transcriptional activity so as to upregulate the expression of its target NAMPT. Studies further indicated that hsa_circ_0005105 can inhibit the expression of type II collagen and aggrecan, promote the expression of MMP-13 and ADAMTS-4, and the generation of PGE2, IL-6, and IL-8, but the linear sequence of hsa_circ_0005105 cannot. MiR-26a has the opposite effect, and hsa_circ_0005105 can antagonize the function of miR-26a. When NAMPT expression was downregulated, the above function of hsa_circ_0005105 was significantly weakened. Therefore, hsa_circ_0005105 can promote extracellular matrix (ECM) degradation by regulating the expression of miR-26a target NAMPT. These findings will provide new targets for treatment and prevention of OA and other orthopedic diseases.

Wu Y ，Zhang Y ，Zhang Y ，Wang JJ ... -  《-》

Circular RNA circ_0128846 promotes the progression of osteoarthritis by regulating miR-127-5p/NAMPT axis.

Liu C ，Cheng P ，Liang J ，Zhao X ，Du W ... -  《-》

Circular RNA Atp9b, a competing endogenous RNA, regulates the progression of osteoarthritis by targeting miR-138-5p.

Osteoarthritis (OA) is the most common joint disease and is mainly characterized by degradation of the articular cartilage. Recently, circular RNAs (circRNAs), novel noncoding RNAs with different biological functions and pathological implications, have been reported to be closely associated with various diseases. Growing evidence indicates that circRNAs act as competing endogenous RNAs (ceRNAs) that bind with microRNAs (miRNAs) and regulate their downstream functions. Here, we identified a new circRNA, circRNA_Atp9b, and further investigated its function in OA using a well-established mouse chondrocyte model. We demonstrated that circRNA_Atp9b expression was significantly up-regulated in mouse chondrocytes after stimulation with interleukin-1 beta (IL-1β), and that knockdown of circRNA_Atp9b promoted the expression of type II collagen while inhibiting the generation of MMP13, COX-2 and IL-6. Moreover, there was a negative correlation between the expression levels of circRNA_Atp9b and microRNA (miR)-138-5p, indicating that miR-138-5p also played a role in IL-1β-induced chondrocytes. Bioinformatics analysis predicted circRNA_Atp9b directly target miR-138-5p, which was validated by dual-luciferase assay. Further functional experiments revealed that down-regulation of miR-138-5p partly reversed the effects of circRNA_Atp9b on extracellular matrix (ECM) catabolism and inflammation. Taken together, these results suggest that circRNA_Atp9b regulates OA progression by modulating ECM catabolism and inflammation in chondrocytes via sponging miR-138-5p. Our findings provide novel insight into the regulatory mechanism of circRNA_Atp9b in OA and may contribute to establishing potential therapeutic strategies.

Zhou ZB ，Du D ，Huang GX ，Chen A ，Zhu L ... -  《-》

CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression.

Osteoarthritis (OA) is a chronic degenerative disease characterized by degeneration and injury of articular cartilage. Circular RNA_SEC24A (circ_SEC24A; circBase ID: hsa_circ_0005105) is upregulated and promotes multiple tumor processes. However, its role in OA progression remained mostly unknown. Quantitative real-time PCR (qRT-PCR) was used to detect the RNA expression of circ_SEC24A, miR-26b-5p and DNA methyltransferase 3 alpha (DNMT3A). Cell proliferation was verified by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Flow cytometry was used to detect apoptosis. Western blot was used to detect protein expression of DNMT3A, proliferating cell nuclear antigen (PCNA), extracellular matrix (ECM) proteins (Collagen II and Aggrecan), and ECM degrading enzymes (matrix metalloproteinase-13 [MMP13] and metallopeptidase with thrombospondin type 1 motif 5 [ADAMTS5]). The target relationship between miR-26b-5p and circ_SEC24A or DNMT3A was predicted by Statbase3.0 or TargetScan and confirmed by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation. Circ_SEC24A was upregulated in osteoarthritic cartilage tissues and IL-1β-induced chondrocytes, accompanying with miR-26b-5p downregulation and DNMT3A upregulation. Circ_SEC24A expression was resistant to RNase R digestion and mainly expressed in the cytoplasm. Interfering circ_SEC24A abolished IL-1β-induced effects on proliferation inhibition, apoptosis, and ECM degradation in chondrocytes, but overexpressing circ_SEC24A had the opposite effects. Inhibiting miR-26b-5p counteracted but upregulating miR-26a-5p mimicked the functions of circ_SEC24A silencing. Reinforcing DNMT3A reversed miR-26b-5p overexpression's role in IL-1β-induced chondrocytes. Mechanically, circ_SEC24A and DNMT3A were competitive endogenous RNAs (ceRNAs) for miR-26b-5p. Circ_SEC24A was a promoting factor for IL-1β-induced OA progression via circ_SEC24A/miR-26b-5p/DNMT3A ceRNA axis.

Zhang Z ，Yang B ，Zhou S ，Wu J ... -  《-》

Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R.

Li BF ，Zhang Y ，Xiao J ，Wang F ，Li M ，Guo XZ ，Xie HB ，Xia H ，Chen B ... -  《-》