Accurate simulation of the herniated cervical intervertebral disc using controllable expansion: a finite element study.

Expansions were carried out in finite element (FE) models of disc hernia including symmetric (median, lateral, paramedian) and asymmetric types. In all models, lubricous disk bulging that applied a linear compression to the anterior part of the cord was observed at the posterior surfaces of the expansion zone, respectively. The shape and position of protrusions varyed with the temperature, magnitude, and location of expanding elements. The geometric deformation and stress distribution of the spinal cord increased as the extent of compression grew. This method is in possession of enormous potential in promoting further individualized research of cervical spondylotic myelopathy.

Neuregulin­1 impacting bone marrow mesenchymal stem cell migration is conducive to functional recovery following spinal cord injury.

The present study was designed to investigate the effect of neuregulin­1 (NRG1) on the migration of rat bone marrow mesenchymal stem cells (BMSCs) and evaluate the role of NRG1 in the functional recovery following spinal cord injury (SCI). Firstly, the effect of NRG1 on the mRNA expression of Snail in the BMSCs was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis; secondly, the BMSCs were transfected with a Snail­overexpression plasmid (pBabe­puro­Snail) and the expression levels of Snail and matrix metalloptoreinase­2 (MMP­2) were detected by RT­qPCR and western blot analyses; thirdly, the cell proliferation and migration of BMSCs modified with pBabe­puro­Snail were detected by methyl thiazolyl tetrazolium and migration assays, respectively; finally, functional recovery of SCI was assessed using the Basso, Beattie, and Bresnahan rating scales. The results showed that NRG1 concentration­dependently promoted the expression of Snail with a peak at 40 ng/ml and 48 h; NRG1 enhanced the promoting effect of Snail on the expression of MMP­2; the overexpression of Snail did not enhance the cell growth of the BMSCs. The NRG1­modified BMSCs promoted the functional recovery of SCI. These results suggested that NRG1 significantly promoted the expression of MMP­2 by upregulating the expression of Snail, and enhanced cell migration of the BMSCs conducive to the functional recovery of SCI.

MicroRNA-210 promotes sensory axon regeneration of adult mice in vivo and in vitro.

Axon regeneration as a critical step in nerve repairing and remodeling after peripheral nerve injury relies on regulation of gene expression. MicroRNAs are emerging to be important epigenetic regulators of gene expression to control axon regeneration. Here we used a novel in vivo electroporation approach to transfect microRNA-210 (miR-210) or siRNAs to adult mice dorsal root ganglion (DRG) neurons, measured the axon length 3days after sciatic nerve crush or dissociated DRG cultures in vitro to detect the effect of miR-210 in sensory axon regeneration. Importantly, we found that miR-210 overexpression could promote sensory axon regeneration and inhibit apoptsosis by ephrin-A3 (EFNA3). In addition, inhibition of endogenous miR-210 in DRG neurons impaired axon regeneration in vitro and in vivo, the regulatory effect of miR-210 was mediated by increased expression of EFNA3 because downregulation of EFNA3 fully rescued axon regeneration. We thus demonstrate that miR-210 is a new physiological regulator of sensory axon regeneration, and EFNA3 may be the functional target of miR-210. We conclude that miR-210 may play an important role in sensory axon regeneration.

Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord.

Lithium has been shown to inhibit apoptosis of neural progenitor cells (NPCs) and promote differentiation of NPCs. However, there was rare data to discuss the effects of lithium on neural differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential promotion of lithium to MSC proliferation and neural differentiation in vitro and after transplanted into the ventral horn of rat spinal cord in vivo. We found that lithium possesses the ability to promote proliferation of GFP-MSCs in a dose dependent manner as verified by growth curve and bromodeoxyuridine (BrdU) incorporation assays; While in neural induction medium, lithium (0.1 mM) promotes neural differentiation of GFP-MSCs as verified by immunostaining and quantitative analysis. After transplantation of GFP-MSCs into the rat spinal cord, lithium treatment enhanced cell survival and neural differentiation after transplantation as verified by immunohistochemistry. These data suggested that lithium could be a potential drug to augment the therapeutic efficiency of MSCs transplantation therapy in central nervous system (CNS) disorders.

Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA-338-3p.

Osteoporosis is a disease characterized by loss of bone mass and degeneration of the microstructure of bone. Resveratrol (3,5,4-tri-hydroxystilbene; RESV) may delay the onset of a variety of age-related diseases. In the present study, an ovariectomized female rat model was used to detect the changes in microRNAs (miRNAs/miRs) following RESV treatment. Subsequently, the target genes of miRNA were predicted using TargetScan software and determined using a dual-luciferase reporter assay. Finally, the role of miR-338-3p in the proliferation and differentiation of human osteoblast (HOB) cells was confirmed. The predominant finding of the present study was the identification of an intact mechanism of the effect of RESV in osteoporosis treatment. The results suggested that RESV suppresses miR-338-3p, followed by an increase in the expression of runt-related transcription factor 2 in HOB cells.

Association between the expression of aggrecan and the distribution of aggrecan gene variable number of tandem repeats with symptomatic lumbar disc herniation in Chinese Han of Northern China.

STUDY DESIGN: Case-control study. OBJECTIVE: To examine the association between the expression of aggrecan and the aggrecan gene variable number of tandem repeats (VNTR) polymorphism with symptomatic lumbar disc herniation (LDH) in Chinese Han of Northern China. SUMMARY OF BACKGROUND DATA: Aggrecan fragments have been found in human degenerated discs, and an association between the aggrecan VNTR polymorphism and intervertebral disc degeneration has been previously reported in middle-aged Finnish men. However, the relationship between the munity of symptomatic LDH with the expression of aggrecan and aggrecan gene VNTR has not been well studied. METHODS: The disease group consisted of 70 patients already diagnosed with symptomatic LDH. The control group consisted of 14 patients restricted to spinal trauma and 113 healthy blood donors without symptoms of LDH who were not diagnosed with LDH. Disc tissue samples were obtained from surgical operations, and blood samples were donated from all participants. The aggrecan expression in isolated tissues was assessed by Western blot using specific antibodies. The aggrecan gene VNTR region was analyzed by polymerase chain reaction. RESULTS: The aggrecan expression positive rate of control group was statistically and significantly higher (P < 0.001) than that of the disease group. Moreover, there was a statistically significant higher frequency of allele 25 or allele 21 in disease group compared with controls (P(A25) = 0.003416 and P(A21) = 0.000716). Compared with the participants with 2 alleles > 25 repeats, subjects with 1 or 2 alleles < or = 25 repeats statistically and significantly overrepresented the disease group without the expression of aggrecan (P < 0.001). CONCLUSION: The findings suggest a relation between aggrecan and symptomatic LDH, where symptomatic LDH has a lower tendency of allele repeats. In addition, this study observed an association between the distribution of aggrecan gene VNTR polymorphism and the expression of aggrecan in symptomatic LDH.

Effect of fluvastatin on vascular endothelial growth factor in rats with osteoporosis in process of fracture healing / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To explore the effect of fluvastatin on vascular endothelial growth factor (VEGF) in rats with osteoporosis in the process of fracture healing.</p><p><b>METHODS</b>Fractures at the intermediate piece of the femur were made on 72 Sprague Dawley (SD) rats (weighing initially 290-340 g and aged 6 months) with osteoporosis after ovariectomy for three months, then these rats were divided randomly into the medication administration group (the experimental group) and the control group, 36 rats each. In the experimental group, the rats received fluvastatin lavage (10 mg/kg per day) since the next day of operation lasting for 6 weeks, and the rats in the control group received placebo. Then the expression of VEGF and VEGF mRNA in bony callus of the two groups was measured respectively with immunohistochemistry and in situ hybridization on days of 3rd, 7th, 14th, 21st, 28th, and 42nd, and image analysis was made with real-color image analysis machine.</p><p><b>RESULTS</b>No difference was found in the cellular localization of VEGF and VEGF mRNA gene expression between the experimental group and the control group in process of fracture healing and their expression modes were almost similar. On the 14th day postoperatively, the positive extent of positive cells in the experimental group was higher than that of the control group (P < 0.05).</p><p><b>CONCLUSION</b>Fluvastatin can promote the VEGF level in rats with osteoporosis in process of fracture healing.</p>

[The expression characteristics and biological significance of nuclear factor- kappa B in mice bone tissue of experimental osteoporosis models].

OBJECTIVE: To study the expression characteristics and biological significance of nuclear factor NF-kappaB p50 and NF-kappaB p65 in osteoporosis development. Adult mice were ovariectomized as models of experimental osteoporosis. In this way, we can explore the molecular mechanism of osteoporosis and understand the significance during the morbility of osteoporosis. METHODS: Four-month female BALB/c mice were randomly divided into ovariectomized group and sham-operated group. 12 weeks after surgery, the mice were sacrificed after the measurement of bone mineral density (BMD). The NF-kappaB level in bone tissue were determined by immunohistochemistry and in situ hybridization techniques. RESULTS: Compared with the sham-operated group, bone density, rarefaction of trabecula and the number of osteoblast decreased in the ovariectomized group, while the number of osteoclast increased in the ovariectomized group. The immunohistochemistry showed that NF-kappaB expressed in both groups. It mainly localized in the cytoplasm of osteoblast, osteocytes and marrow stroma cell. The expression level in the ovariectomized group was higher than that in the sham-operated group and was negatively correlated with the BMD (P < 0.01 or P < 0.05). In situ hybridization demonstrated that the expression levels of NF-kappaB 50mRNA and NF-kappaB 65mRNA in ovariectomized group were significantly higher than that of the sham-operated group (P < 0.05). CONCLUSION: The expression level of NF-kappaB significantly increased in the bone tissue of ovariectomized mice, and its abnormal expression was significantly correlated with BMD.