Over-expression of hsa_circ_0088214 suppresses tumor progression by inhibiting Akt signaling pathway in osteosarcoma.

BACKGROUND: To explore the effect of has_circ_0088214 in osteosarcoma cells and corresponding mechanisms. METHODS: Osteosarcoma cell line MG63 and U2OS were selected in this study. Wound-healing and matrigel transwell assays were performed to detect migration and invasion capacities. CCK-8 assay was used to measure cell growth and cisplatin resistance. Cell apoptosis was observed by Hoechst 33342 staining after H2O2 induce. Western Blot was used to detect protein expression level. The rescue experiments were also performed using an Akt activator SC79. RESULTS: Hsa_circ_0088214 was down-regulated in osteosarcoma cells compared to normal osteoblast cells. Over-expression of has_circ_0088214 significantly reduced osteosarcoma cells invasion, migration and resistance to cisplatin, but the apoptotic ratio was increased. The phosphorylation level of Akt could be regulated by hsa_circ_0088214, and rescue experiments proved Akt signaling pathway took part in above biological processes. CONCLUSION: Up-regulation of hsa_circ_0088214 suppresses invasion, migration, cisplatin resistance but promoting apoptosis induced by H2O2 by inhibiting Akt signaling pathway in osteosarcoma.

Percutaneous Spinal Endoscopic Combined with Thoracoscopic Surgery for Treatment of Thoracic Eden IV Dumbbell Tumors.

OBJECTIVE: Thoracic Eden IV dumbbell tumors are rare conditions characterized by neoplasms that arise from neurogenic elements, with intraforaminal and posterior mediastinal involvement. Surgical resection is commonly performed to treat thoracic Eden IV dumbbell-shaped tumors. The combined thoracic-neurosurgical approach is a routine surgical procedure according to the literature. We present our experience with resection of thoracic Eden IV dumbbell tumors with combined percutaneous spinal endoscopic and thoracoscopic procedures in a single stage. METHODS: A retrospective review of 7 patients undergoing spinal endoscopic combined with thoracoscopic surgery for thoracic Eden IV dumbbell tumors was performed in our department between 2017 and 2020. Patient demographics, clinical features, operative reports, and preoperative and postoperative images were reviewed. RESULTS: Complete resection was achieved in the 7 cases. The mean operative time was 207 minutes (range, 160-310 minutes), with mean estimated blood loss of 47 mL (range, 20-80 mL). The mean chest drain duration was 3 days (range, 2-4 days), and the mean hospital stay was 7 days (range, 5-8 days). No operative complications were observed. During the follow-up period, there were no obvious complications, tumor recurrence, or spinal instability. CONCLUSIONS: Percutaneous spinal endoscopic combined with thoracoscopic surgery for the treatment of Eden IV type thoracic dumbbell tumors is a novel, safe, and effective surgical method that can not only remove tumors inside and outside of the thoracic intervertebral foramen in a single stage but also minimize damage to the normal structure of the spine and help in early recovery.

Co-Transplantation of Human Umbilical Cord Mesenchymal Stem Cells and Human Neural Stem Cells Improves the Outcome in Rats with Spinal Cord Injury.

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) are promising graft materials for cell therapies in spinal cord injury (SCI) models. Previous studies have demonstrated that MSCs can regulate the microenvironment of NSCs and promote their survival rate. Furthermore, several studies indicate that MSCs can reduce stem cell transplantation-linked tumor formation. To our knowledge, no previous studies have determined whether co-transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and human neural stem cells (hNSCs) could improve the outcome in rats with SCI. Therefore, we investigated whether the transplantation of hUC-MSCs combined with hNSCs through an intramedullary injection can improve the outcome of rats with SCI, and explored the underlying mechanisms. In this study, a moderate spinal cord contusion model was established in adult female Wistar rats using an NYU impactor. In total, 108 spinal cord-injured rats were randomly selected and divided into the following five groups: 1) hUC-MSCs group, 2) hNSCs group, 3) hUC-MSCs+hNSCs group, 4) PBS (control) group, and 5) a Sham group. Basso, Beattie and Bresnahan (BBB) behavioral test scores were used to evaluate the motor function of all animals before and after the SCI weekly through the 8th week. Two weeks after transplantation, some rats were sacrificed, immunofluorescence and immunohistochemistry were performed to evaluate the survival and differentiation of the transplanted stem cells, and brain-derived neurotrophic factor (BDNF) was detected by ELISA in the injured spinal cords. At the end of the experiment, we evaluated the remaining myelin sheath and anterior horn neurons in the injured spinal cords using Luxol Fast Blue (LFB) staining. Our results demonstrated that the surviving stem cells in the hUC-MSCs+hNSCs group were significantly increased compared with those in the hUC-MSCs alone and the hNSCs alone groups 2 weeks post-transplantation. Furthermore, the results of the BBB scores and the remaining myelin sheath evaluated via LFB staining in the injured spinal cords demonstrated that the most significantly improved outcome occurred in the hUC-MSCs+hNSCs group. The hUC-MSCs alone and the hNSCs alone groups also had a better outcome compared with that of the PBS-treated group. In conclusion, the present study demonstrates that local intramedullary subacute transplantation of hUC-MSCs, hNSCs, or hUC-MSCs+hNSCs significantly improves the outcome in an in vivo moderate contusion SCI model, and that co-transplantation of hUC-MSCs and hNSCs displayed the best outcome in our experiment.

Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway.

Silicon is essential for bone formation. A low-silicon diet leads to bone defects, and numerous animal models have demonstrated that silicon supplementation increases bone mineral density (BMD) and reduces bone fragility. However, the exact mechanism of this action has not been characterized. In this study, we aimed to determine the role of biological silicon in the induction of osteoblast differentiation and the possible underlying mechanism. We examined whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related transcription factor 2 (RUNX2) signaling pathway by investigating its effect in vitro at several concentrations on COL-1 and osteocalcin synthesis in human osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins was detected by Western blotting following exposure to noggin, an inhibitor of BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2. Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 µM orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2, COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the formation of mineralized nodules were also observed under these conditions. Furthermore, preconditioning with noggin inhibited the silicon-induced upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP-2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic differentiation of rat BMSCs.