LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels.

BACKGROUND: Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. METHODS: sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and ß-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. RESULTS: We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. CONCLUSIONS: LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Clinical outcomes of treatment with cage-shaped demineralized bone plus local bone grafts vs. autogenous iliac crest bone grafts in instrumented single-level lumbar fusion: A retrospective cohort study.

The aim of the present study was to compare the clinical outcomes of cage-shaped demineralized bone plus local bone grafts (CDBLG) with those of autogenous iliac crest bone grafts (ICBG) implanted for the treatment of single-level lumbar intervertebral disc degenerative diseases. A total of 69 cases of degenerative spinal disorder treated between January 2011 and December 2013 were retrospectively analyzed. Of these, 44 were treated with CDBLG and 25 with autogenous ICBG. All fusions were instrumented single level. Fusion was assessed after 6, 12 and 24 months by X-ray and CT scans post-operatively. Clinical outcomes were determined during follow-up and assessments included the Oswestry Disability Index, Visual Analogue Scale for back and leg pain and the Short Form-36 general health survey physical component summary. The results indicated that the overall fusion rate at 24 months post-operatively was higher in the ICBG group compared with that in the CDBLG group, although not significantly (P>0.05). All other outcome measures were significantly improved in the two groups after the surgery (P<0.05), but no significant differences were observed between the two groups (P>0.05). Blood loss and mean duration of surgery in the CDBLG group were significantly lower compared with those in the ICBG group (P<0.05). In conclusion, CDBLG achieved a similar fusion rate and clinical outcome as ICBG but was associated with significantly reduced blood loss and mean duration of surgery. In conclusion, the present study provided CDBLG bone graft as an alternative option for single-level fusion.

Corosolic acid inhibits the proliferation of osteosarcoma cells by inducing apoptosis.

Corosolic acid (CRA), a pentacyclic triterpene isolated from medicinal herbs, has been reported to exhibit anticancer properties in several cancers. However, the anticancer activity of CRA in osteosarcoma cells is still unclear. In the present study, the inhibitory effect of CRA in osteosarcoma MG-63 cells was investigated, and the results revealed that CRA significantly inhibited the viability of MG-63 cells in a dose- and time-dependent manner. A typical apoptotic hallmark such as DNA ladder was detected by agarose gel electrophoresis following treatment with CRA. Further experiments demonstrated that CRA induced apoptosis of MG-63 cells by flow cytometry using propidium iodide and annexin V staining. In addition, it was observed that the apoptosis of MG-63 cells induced by CRA was closely associated with activation of caspase-3 and caspase-9, loss of mitochondrial membrane potential, and release of cytochrome c from mitochondria, suggesting that CRA may trigger the activation of the mitochondria-mediated apoptosis pathway. In addition, the inhibition of caspase activity attenuated the CRA-induced apoptosis of MG-63 cells, which further confirmed the role of the mitochondrial pathway in CRA-induced apoptosis. These results indicated that CRA could induce the apoptosis of osteosarcoma cells through activating the mitochondrial pathway, which provides an evidence that CRA may be a useful chemotherapeutic agent for osteosarcoma.

Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling.

[The design of inferior rectus abdominis flap and its study of applied anatomy].

OBJECTIVE: To describe the anatomy of inferior epigastric artery and its correlation with rectus abdominis muscle in order to provide anatomical basis for reconstruction of defect in the oral and maxillofacial region. METHODS: 10 Chinese adult specimens fixed by 10% formalin were simulated for the design of inferior rectus abdominis flap, and then observing, taking a photograph during the cadavers were being operated and measuring by image analysis software in the end. RESULTS: The original external diameters of inferior epigastric artery and length of its trunk were (2.58 +/- 0.60) mm and (85.87 +/- 14.90) mm respectively. Its perforators distribute intensively toward hilum. CONCLUSION: Whether rectus abdominis myocutaneous flap or deep inferior epigastric perforator flap adapts to reconstruct the defect of oral and maxillofacial region due to invariable traveling of inferior epigastric artery and its wide original external diameters relatively.