bims-mirbon 2021-12-19 papers

Issue of 2021–12–19
five papers selected by
Japneet Kaur, Mayo Clinic

Bioengineered. 2021 Dec 13.

Long non-coding RNA musculin antisense RNA 1 promotes proliferation and suppresses apoptosis in osteoarthritic chondrocytes via the microRNA-369-3p/Janus kinase-2/ signal transducers and activators of transcription 3 axis.

Zhenyu Tang, Zongming Gong, Xiaoliang Sun.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in osteoarthritis (OA). The present study aimed to investigate the underlying molecular mechanism of lncRNA musculin antisense RNA 1 (MSC-AS1) in OA. RT-qPCR was used to detect MSC-AS1 levels in cartilage tissues from patients with OA. The effects of MSC-AS1 knockdown on the viability and apoptosis in OA were evaluated via CCK-8 and TUNEL assays. The StarBase database was used to predict the binding sites between microRNA (miR)-369-3p and MSC-AS1 or JAK2, which were confirmed via the dual-luciferase reporter assay. The results demonstrated that MSC-AS1 expression was downregulated in OA. Functional analysis indicated that the addition of MSC-AS1 promoted viability and inhibited inflammation and the apoptosis of chondrocytes. In addition, MSC-AS1 regulated the survival of OA chondrocytes by sponging miR-369-3p. JAK2 was confirmed as a direct target of miR-369-3p, and MSC-AS1 regulated JAK2/STAT3 signaling via miR-369-3p in OA chondrocytes. Taken together, our results suggest that MSC-AS1 may regulate the miR-369-3p/JAK2/STAT3 signaling pathway to accelerate the viability, and inhibit inflammation and cell apoptosis in OA chondrocytes.

Keywords: JAK2; STAT3; microRNA-369-3p; musculin antisense RNA 1; osteoarthritis

DOI: https://doi.org/10.1080/21655979.2021.2013028

Bioengineered. 2021 Dec 13.

Exosomal microRNA-150-5p from bone marrow mesenchymal stromal cells mitigates cerebral ischemia/reperfusion injury via targeting toll-like receptor 5.

Shuo Yang, Xue Li, Ting Bi.

MicroRNA (miR)-150-5p has been investigated in many studies, while the role of exosomal miR-150-5p from bone marrow mesenchymal stromal cells (BMSCs) on cerebral ischemia/reperfusion (I/R) injury is not fully explored. This research aims to probe the effects of exosomal miR-150-5p from BMSCs on cerebral I/R injury via regulating B-cell translocation gene 2 (TLR5). BMSCs were cultured and transfected with miR-150-5p mimic, then exosomes from BMSCs were extracted. The middle cerebral artery occlusion (MCAO) rat model was established, and miR-150-5p and TLR5 levels in rat brain tissues were detected. Then, gain and loss-function assays were conducted to determine the impact of exosomes, miR-150-5p and TLR5 on neurological function, pathological changes, neuron apoptosis and inflammatory factors of MCAO rats. The binding relation between miR-150-5p and TLR5 was validated. It was found that miR-150-5p expression was decreased while TLR5 level was augmented in MCAO rats. The exosomes from BMSCs could improve neurological function, pathological changes, decelerate neuron apoptosis and reduce inflammatory factors in MCAO rats. Enriched miR-150-5p or decreased TLR5 could enhance the protective effects of exosomes from BMSCs on cerebral I/R injury. The elevated TLR5 reversed the impacts of elevated exosomal miR-150-5p. TLR5 was targeted by miR-150-5p. This research manifested that exosomal miR-150-5p from BMSCs exerts protective effects on cerebral I/R injury via repressing TLR5. This study provided novel therapeutic targets for the treatment of cerebral I/R injury.

Keywords: Biological function; Bone marrow mesenchymal stromal cells; Cerebral ischemia/reperfusion injury; Exosomes; MicroRNA-150-5p; Toll-like receptor 5

DOI: https://doi.org/10.1080/21655979.2021.2012402

Cell Biochem Funct. 2021 Dec 17.

Advances on biological functions of exosomal non-coding RNAs in osteoarthritis.

Jialei Chen, Xi Yu, Xiang Zhang.

Exosomes can be secreted by various cells and function as intercellular communication vehicles by delivering specific cargoes from the donor cells to the recipient cells through their paracrine activity. Recently, an increasing number of studies have shown that non-coding RNAs (ncRNAs) could be entrapped in and transferred between cartilage-related cells as exosomal cargoes to modulate the expression of various target genes by regulation at post-transcriptional and post-translational levels. They are mainly comprised of microRNAs, long non-coding RNAs, and circular RNAs. Articular cartilage degeneration is one of the main pathological features of osteoarthritis. Exosomal ncRNAs are involved in pathological processes of osteoarthritis, such as proliferation, migration, chondrogenesis, chondrocyte differentiation induction, extracellular matrix formation, apoptosis, and inflammation. In this review, we summarize the biological functions of exosomal ncRNAs in cartilage homeostasis and osteoarthritis progression and discuss the perspectives and challenges of exosomal ncRNAs application for osteoarthritis patients in the future. Exosomal ncRNA has an important regulatory role in the pathogenesis of osteoarthritis, but more evidence is needed for clinical application.

Keywords: circular RNA; exosomes; long non-coding RNA; microRNA; non-coding RNA; osteoarthritis

DOI: https://doi.org/10.1002/cbf.3679

J Healthc Eng. 2021 ;2021 2793379

Circular RNA mmu_circ_0001598 Contributes to IL-1β-Induced Osteoarthritis Progression by Regulating miR-127-3p.

Xierenguli Apizi, Dilibaier Talifujiang, Aziguli Kasimu, Xue Zhang, Aibibula Yiming, Xin Ma, Qingshan Song, Dequan Wang.

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. In this study, we found that circ_0001598 was significantly upregulated in chondrocytes treated with IL-1β and in cartilage tissue from mice with severed anterior cruciate ligament surgery (ACLT) induced OA models. Interference with circ_0001598 in vitro restored IL-1β-induced chondrocyte proliferation and apoptosis. Silencing circ_0001598 significantly alleviated ACLT-induced OA in mice. Mechanistically, knockdown of circ_0001598 affected chondrocyte proliferation, apoptosis, and matrix degradation by regulating miR-127-3p. Taken together, our results demonstrate the fundamental role of circ_0001598 and provide new ideas for the prevention and treatment of osteoarthritis.

DOI: https://doi.org/10.1155/2021/2793379

Toxicol In Vitro. 2021 Dec 09. pii: S0887-2333(21)00222-8. [Epub ahead of print] 105297

Circular RNA PVT1 inhibits tendon stem/progenitor cell senescence by sponging microRNA-199a-5p.

Weifeng Han, Xu Tao, Tujun Weng, Lei Chen.

Tendon stem/progenitor cell (TSPC) senescence can lead to age-dependent tendon maladies and undermines both tendon repair and replacement capacity in humans. The mechanisms underlying TSPC senescence and sensitivity to adverse factors are complicated. In this study, we analyzed involvement of the circular RNA (circRNA) PVT1 (circPVT1) in TSPC senescence. circPVT1 expression was found to be significantly diminished in human TSPCs under prolonged in vitro culture. Accordingly, circPVT1 knockdown promoted senescence progression and suppressed self renewal, migration, and tenogenic differentiation of TSPCs. Furthermore, we found that circPVT1 directly targets microRNA (miR)-199a-5p thereby attenuating its negative regulation of SIRT1 expression. Either miR-199a-5p inhibition or SIRT1 overexpression attenuated the senescence-boosting effect of circPVT1 knockdown, implying that circPVT1 suppresses TSPC senescence in part by upregulating the miR-199a-5p-SIRT1 signaling axis. Our findings conclusively explain the major roles of circPVT1 in TSPC senescence regulation; circPVT1 is a novel potential therapeutic target for reducing tendon senescence.

Keywords: SIRT1; Senescence/aging; Tendon stem/progenitor cells; circPVT1; miR-199a-5p

DOI: https://doi.org/10.1016/j.tiv.2021.105297