Objectives As a new molecular marker and therapeutic target, Piwi-interacting RNA(piRNA) has been widely studied in the field of oncology, but few people have studied the role of piRNA in osteoarthritis. Here, we found that the expression of hsa_piR_019914 in human osteoarthritis cartilage decreased significantly. We studied the relationship between hsa_piR_019914 and gene expression in osteoarthritis cartilage and the role of hsa_piR_019914 in chondrocyte biology. It is suggested that hsa_piR_019914 may be a new target for the treatment of osteoarthritis. Design Using the GEO database to analyze the expression of piRNA in the cartilage of osteoarthritis, using qPCR to detect the effect of inflammatory factors on the expression of piRNA in chondrocytes, using CCK-8 and clone formation to detect the effect of hsa_piR_019914 on chondrocyte proliferation, and using flow cytometry to detect the effect of hsa_piR_019914 on chondrocyte apoptosis and ROS production. The target gene of hsa_piR_019914 regulation was detected by mRNA sequencing. Results GEO data analysis found that 11 piRNAs were downregulated in cartilage tissue of osteoarthritis, and inflammatory factors inhibited the expression of hsa_piR_019914 in chondrocytes. Hsa_piR_019914 promoted the proliferation of chondrocytes and the synthesis of extracellular matrix. Hsa_piR_019914 inhibited the apoptosis of chondrocytes and the expression of cell-matrix protease. Hsa_piR_019914 targets regulating the expression of LDHA and inhibiting the production of ROS. Conclusions This work highlights the role of hsa_piR_019914 in chondrocyte metabolism, the inhibition of LDHA, and the reduction of ROS production, which may be used as a potential treatment for osteoarthritis.
BackgroundTo date, no in-depth study has been conducted on the intrinsic pathological relationship between altered brain activity and related behavioral changes in patients with orbital fracture (OF).PurposeThe present research aimed to explore the potential functional network cerebrum activities in patients with OF using resting state functional magnetic resonance imaging–fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF). This technique can reveal dynamic functional changes in specific cerebrum areas.MethodsTwenty patients with OF and 20 healthy controls (HCs) were included, closely matched in terms of gender, age, weight, and education level. To record spontaneous cerebral activity changes, the rsfMRI-fALFF tool was applied. Receiver operating characteristic (ROC) curves and Pearson's correlation analysis were used to analyze mean fALFF values in specific cerebrum regions and to explore changes of behavioral changes in patients with OF. The Hospital Depression and Anxiety scale was applied to reveal the relationship between emotional states and fALFF values of the right superior temporal gyrus in patients with OF.ResultsIn comparison with HCs, significantly lower fALFF values were detected in the left anterior cingulate gyrus (LACG) and right superior temporal gyrus (RSTG) in patients with OF. ROC curve analysis showed excellent accuracy. The mean fALFF values of the RSTG negatively correlated with the depression score as well as the anxiety score.ConclusionThe finding of abnormal spontaneous activities in cerebral regions may contribute to more comprehensive understanding of the potential neural network changes in patients with OF. The changes of fALFF value in patients with OF may help to gauge their emotional changes and clinical recovery levels.
Objectives Osteoarthritis (OA) is the most common joint disease. The occurrence and progression of OA are regulated by epigenetics. A large number of studies have shown the important regulatory role of noncoding RNAs in joint diseases. As the largest class of noncoding small RNAs, the importance of piRNAs in many diseases, especially cancer, has been increasingly recognized. However, few studies have explored the role of piRNAs in OA. Our study showed that hsa_piR_019914 decreased significantly in OA. This study aimed to demonstrate the role of hsa_piR_019914 as a potential biological target of OA in chondrocytes. Design The GEO database and bioinformatics analysis were used for a series of screenings, and the OA model using human articular chondrocytes (C28/I2 cells), SW1353 cells under inflammatory factor stimulation was used to determine that hsa_piR_019914 was significantly downregulated in OA. Overexpression or inhibition of hsa_piR_019914 in C28/I2 cells was achieved by transfecting mimics or inhibitors. The effect of hsa_piR_019914 on the biological function of chondrocytes was verified by qPCR, flow cytometry, and colony formation assays in vitro. The target gene of hsa_piR_019914, lactate dehydrogenase A (LDHA), was screened by small RNA sequencing and quantitative polymerase chain reaction (qPCR), LDHA was knocked out in C28/I2 cells by the transfection of siRNA LDHA, and the relationship between hsa_piR_019914, LDHA, and reactive oxygen species (ROS) production was verified by flow cytometry. Results The piRNA hsa-piR-019914 was significantly downregulated in osteoarthritis (OA). Hsa-piR-019914 reduced inflammation-mediated chondrocyte apoptosis and maintained cell proliferation and clone formation in vitro. Hsa-piR-019914 reduced the production of LDHA-dependent ROS through targeted regulation of LDHA expression, maintained chondrocyte-specific gene expression of ACAN and COL2, and inhibited the gene expression of MMP3 and MMP13. Conclusions Collectively, this study showed that hsa_piR_019914 was negatively correlated with the expression of LDHA, which mediates ROS production. Under the stimulation of inflammatory factors, overexpression of hsa_piR_019914 had a protective effect on chondrocytes in vitro, and the absence of hsa_piR_019914 exacerbated the negative effect of inflammation on chondrocytes. Studies on piRNAs provide new therapeutic interventions for OA.
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