Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7–ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7–ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.

OBJECTIVE:Spinal cord injury (SCI) is a severe traumatic disease in the central nervous system, and can result in neuronal injury. Altered miRNA expression is identified to be involved in the pathogenesis of SCI.DESIGN:This study investigated the clinical value of miR-142-5p in SCI patients, and explored its functional role in the regulation of inflammatory.SETTING:The First Affiliated Hospital of Soochow University.PARTICIPANTS:Ninety-eight patients with acute spinal trauma.INTERVENTIONS:All patients were recruited, and divided into complete SCI group, incomplete SCI group and normal nerve function group.OUTCOME MEASURES:Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of miR-142-5p. CCK-8 and flow cytometry assay were performed to evaluate the cell viability and apoptosis. ELISA assay was applied to estimate the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).RESULTS:Serum miR-142-5p level was significantly increased in SCI patients, especially the complete SCI cases. ROC curve analysis suggested miR-142-5p could distinguish SCI patients from normal nerve function patients and was associated with the severity of SCI. A positive association was detected between miR-142-5p and serum levels of IL-6, TNF-α in SCI patients. Downregulation of miR-142-5p significantly reduced the protein levels of both IL-6 and TNF-α in LPS treated PC12 cells, and weakened LPS induced cell apoptosis.CONCLUSION:MiR-142-5p is a potential biomarker for the occurrence of SCI in acute spinal trauma patients. Downregulation of miR-142-5p plays an anti-inflammatory effect for SCI patients.

Grass carp reovirus (GCRV) causes grass carp hemorrhage disease and is one of the most damaging factors in the culture of grass carp (Ctenopharyngodon idellus). Until now, the mechanisms underlying GCRV infection have been largely unknown. To explore the molecular responses to GCRV infection in C. idellus kidney (CIK) cells, we used high-throughput sequencing to investigate the circRNA, mRNA, and miRNA expression patterns and the circRNA-miRNA-mRNA network. A total of 76 circRNAs, 798 mRNAs, and 186 miRNAs were identified as differentially expressed (DE) RNAs in GCRV-infected cells compared with uninfected cells, of which 40 circRNAs, 658 mRNAs, and 146 miRNAs were upregulated, and 36 circRNAs, 140 mRNAs, and 40 miRNAs were downregulated (fold change > 2, p < .05). A Gene Ontology (GO) analysis of the DE circRNA parental genes, mRNAs, and miRNA target genes was performed. The parental genes of the DE circRNAs, the DE mRNAs, and the target genes of the DE miRNAs were mainly enriched in metal-ion-binding-, immune-, and DNA-replication-related items, respectively. A KEGG pathway analysis showed that the DE circRNA parental genes, DE mRNAs, and miRNA target genes were predominantly enriched in endocytosis-, immune-, and infection-related pathways, respectively. The miRNA-target interactions were also predicted and competing regulatory networks of endogenous RNAs were constructed based on the DE RNAs. Our prediction results suggest that the circRNA-2780/cik-miRNA-7796/KAT6B, circRNA-1351/cik-miRNA-10648/B2L14 and circRNA-1591/cik-miR-8141/AMPD3 axes may be associated with GCRV infection. This study suggests that the crosstalk between circRNAs and their competing mRNAs play crucial roles in GCRV infection.