Chao Han

Dynamic expression of Runx2, Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats.

Objective:  To study dynamic changes in gene expression and protein synthesis of runt‐related transcription factor‐2 (Runx2), Osterix and AJ18 in the femoral head of steroid‐induced osteonecrosis in rats.

MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-α-induced apoptosis by targeting JunD

BACKGROUND Human nucleus pulposus cell (HNPC) apoptosis plays an important role in the development of intervertebral disc degeneration (IVDD). Our previous research revealed that among all of the dysregulated microRNAs in the degenerated nucleus pulposus tissues of patient with IVDD, miRNA-494 (miR-494) is the most significantly increased. However, the influence of miR-494 HNPC apoptosis has not been confirmed. OBJECTIVE This study was designed to evaluate the effect of miR-494 on the HNPC apoptosis induced by TNF-α and to explore the possible mechanism of this process. METHODS First, HNPCs were stimulated with TNF-α at different concentrations (0 ng/ml, 10 ng/ml, 50 ng/ml, or 100 ng/ml) for 0 h, 8 h, 16 h, or 24 h. Annexin V-PE/7-AAD assays and real-time quantitative PCR were used to detect the cell apoptosis rates and miR-494 expression. Second, we successfully knocked down endogenous miR-494 in HNPCs via lentiviral antigomiR-494 vector infection and then stimulated with TNF-α (100 ng/ml, 16 h). The rates of apoptosis and miR-494 expression were then detected again. Additionally, a dual-luciferase reporter assay and western blotting were used to determine whether JunD is a target of miR-494. Finally, western blotting was used to analyze the expression of cytochrome C. RESULTS We found that the rate of apoptosis increased with concentration, time (p < 0.05) and miR-494 expression (p < 0.05). The rate of apoptosis in the 100 ng/ml, 16 h group appeared to be suitable. After transfection, the apoptosis rate and miR-494 expression were significantly decreased in the antigomiR-494+TNF-α group compared to the controls (p < 0.05). We also revealed that JunD is a target of miR-494. Western blotting analysis demonstrated that treatment with the lentiviral antigomiR-494 vector resulted in increased expression of JunD (p < 0.05) and decreased expression of cytochrome C (p < 0.05). CONCLUSION These results indicated that miR-494 is a novel regulator of HNPC apoptosis induced by TNF-α. The knock-out of miR-494 expression protected the HNPCs from apoptosis via the up-regulation of JunD, which was possibly mediated via cytochrome C apoptotic signaling. These findings suggest that the miR-494/JunD signaling pathway might represent a novel therapeutic target for the prevention of IVDD.

Possible role of autoimmune reaction in Modic Type I changes

Modic changes (MCs) are common abnormalities in the vertebral endplates and adjacent bone marrow, which are visible on magnetic resonance imaging. They are regarded as having a strong association with the clinical symptom of low back pain (LBP). Nevertheless, the general pathogenesis of MCs is still under discussion. MCs can be divided into three types. Type I MCs represent extensive subchondral bone edema and vascular granulation tissue within the bone marrow of the adjacent endplate. The reasons for the edema and vascularization in Type I MCs, which may be the major mechanism underlying LBP, remain unclear. Chronic repetitive shear forces on the endplates lead to local disruption and microfractures. Following a breach of the outer annulus fibrous, the nucleus pulposus (NP) may enter the vertebral body. We hypothesize that the consequent autoimmune response due to a foreign body may cause and promote the development of edema, vascularization and inflammation, which are characteristic of Type I MCs. The production of cytokines evoked by autoimmunity could therefore be responsible for the significant clinical symptoms of LBP. If this underlying etiological pathway is proven, MCs and the consequent LBP could be treated by novel clinical methods.

The use of gabapentin in the management of postoperative pain after total knee arthroplasty: A PRISMA-compliant meta-analysis of randomized controlled trials.

AbstractPain management after total knee arthroplasty (TKA) varies and has been widely studied in recent years. Some randomized controlled studies have carried out to evaluate the effects of gabapentin on pain relief after TKA. However, no solid result was made about it. The purpose of this Meta-Analysis of Randomized Controlled Trials (RCTs) was to estimate the overall effect of pain control of gabapentin versus placebo after a TKA. An electronic-based search using the following databases: PubMed, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trial from 1966 to June 2015. RCTs involving gabapentin and placebo for total knee arthroplasty were included. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Six trials with 859 participants met the inclusion criteria. The primary endpoint was cumulative narcotic consumption and the visual analog scale scores at 12 hours, 24 hours, and 48 hours, postoperatively. The knee flexion degree and treatment side effects were also compiled to evaluate the safety of gabapentin. After testing for the heterogeneity and publication bias among studies, data were aggregated for random-effects modeling when necessary. There was a significant decrease in morphine consumption at 12 hours (MD = –4.69, 95% CI: −7.18 to –2.21, P = 0.0002), 24 hours (MD = –5.30, 95% CI: −9.94 to –0.66, P = 0.03), and 48 hours (MD = –17.80, 95% CI: −31.95 to –3.64, P = 0.01), respectively. Compared with the control group, the rate of pruritus was less in the gabapentin group (RR 0.20, 95% CI 0.10 to 0.38, P = 0.00). In summary, the administration of gabapentin was effective in decreasing postoperative narcotic consumption and the incidence of pruritus. There was a high risk of selection bias and a higher heterogeneity of knee flexion range in this analysis. More high-quality large randomized controlled trials with long follow-up period are necessary for proper comparisons of the efficacy and safety of gabapentin with placebo.Systematic review registration number: No.

An Animal Model of Modic Changes by Embedding Autogenous Nucleus Pulposus inside Subchondral Bone of Lumbar Vertebrae.

The establishment of Modic changes (MCs) in animal model was vital for research of MCs. Fifty-four rabbits were divided into a sham group, a muscle embedment group (ME group) and nucleus pulposus (NP) embedment group (NPE group). In the NPE group, the discs were exposed by the lumbar anterolateral surgical approach. A needle was used to puncture the L5 vertebral body close to the endplate. NP was extracted by a syringe from L1/2 intervertebral discs and then injected into the drilled hole of subchondral bone. The muscle embedment group and sham group had the same procedure and drill method as the NP embedment group. Some pieces of muscle were put into the hole in the ME group, but nothing was put into the hole in the sham group. After the operation, MRI scan and molecular biology tests were applied. The signal changes were found in the NPE group; while the sham group and the ME group showed no significant signal change. Histological observation confirmed that there was abnormal tissue proliferation in imbed site. High expression of IL-4, IL-17 and IFN-γ were detected in the NPE group. The embedment of NP into subchondral bone can create an animal model of MCs.

Interleukin-23 may contribute to the pathogenesis of lumbar disc herniation through the IL-23/IL-17 pathway

BackgroundStudies have indicated that interleukin 23 (IL-23) plays an important role in many inflammatory- and autoimmune-related diseases. However, there is little knowledge about IL-23 in lumbar disc herniation (LDH). Thus, in this study, we aimed to find out whether IL-23 is expressed in intervertebral discs (IVDs) and what roles it may play.MethodsHuman IVD tissues were collected from 29 LDH patients and 8 vertebral fracture patients (normal control, NC group). According to the integrity of annulus fibrosus, LDH patients were divided into two groups: R group (ruptured group, n = 16) and NR group (non-ruptured group, n = 13). Morphological changes of IVDs were assessed by hematoxylin and eosin (HE staining), and expression of IL-23 in IVD tissues was detected by immunohistochemical staining. Besides gene expression of IL-23, IL-17, IL-6, IL-1β, and TNF-α was also evaluated by reverse transcription polymerase chain reaction (RT-PCR).ResultsThe results showed that the R group was more degenerated than the other two groups and NC group showed the least degenerated performance; stronger positive IL-23 expression was observed in herniated IVDs, especially in the R group. Meanwhile, higher gene expression of IL-23, IL-17, IL-6, IL-1β, and TNF-α was found in the tissues from LDH patients and a positive correlation between IL-17 and IL-23 gene expression was also observed.ConclusionsTaken all above results together, it may be deduced that higher expression of IL-23 may contribute to the deterioration of IVDs through the IL-23/IL-17 pathway.

Prevalence of Modic changes in the lumbar vertebrae and their associations with workload, smoking and weight in northern China

The distribution of Modic changes (MCs) in the lumbar endplates and the evaluation of the relationships between MCs and risk factors are vital for research into MCs. The T1-weighted and T2-weighted sagittal MRI scans of 210 patients who exhibited lumbar intervertebral disc degeneration were retrospectively reviewed. The patients’ weights, genders, smoking statuses, physical activity levels and specific types of MC were recorded. The associations between MCs and risk factors, such as physical work, smoking and body mass index, were also analysed. MCs were observed in 47 patients (22.4%), including 16 males and 31 females. Among all patients, the L5/S1 lumbar level was most likely to suffer MCs. The MCs were predominantly type II. MCs occurred more often in obese patients than in normal and overweight patients (P < 0.05). Patients whose jobs required heavy labour were more likely to develop MCs (P < 0.05). Heavy work and obesity were related to type III MCs more strongly than the other types (P > 0.05). Smoking seemed not to be correlated with the incidence of MCs (P > 0.05). Gender, obesity and heavy work were strongly associated with MCs. Biomechanical factors may play a critical role in the development of MCs.

Is pregabalin effective and safe in total knee arthroplasty? A PRISMA-compliant meta-analysis of randomized-controlled trials.

Background: Pain management after total knee arthroplasty (TKA) varies and has been investigated for years. Pregabalin as an anticonvulsant agent that selectively affects the nociceptive process has been used for pain relief after operation. This meta-analysis was conducted to examine the evidence of pregabalin in TKA. Methods: Systematic searches of all related literatures were conducted using the following databases: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Only randomized-controlled trials (RCTs) for TKA were included. The postoperative narcotic requirements, visual analog scale scores, knee flexion range, and relative risk of incidence rate of adverse effects in the pregabalin group versus placebo group were extracted throughout the study. Results: Seven placebo-controlled RCTs met the inclusion criteria. The use of pregabalin significantly decrease the postoperative total morphine consumption (P < .05) and increase the passive knee flexion range (P < .05). Compared with the control group, the incidence of some side effects (nausea, vomiting, pruritus, and constipation) was less in the pregabalin group (P < .05). Conclusions: The administration of pregabalin is not only efficacious in the reduction of narcotic requirements and incidence of some adverse effect, but also workable for the improvement of passive knee flexion range after TKA.

Role of Teriparatide in Glucocorticoid-induced Osteoporosis through Regulating Cellular Reactive Oxygen Species: Teriparatide IN Glucocorticoid-Induced Osteoporosis

To determine the signaling pathways mediated by teriparatide in MLO‐Y4 cell lines based on the evaluation of reactive oxygen species (ROS) through AKT pathways, which regulate apoptosis of bone cells.

The Effect of Obesity on Clinical Outcomes After Minimally Invasive Surgery of the Spine: A Systematic Review and Meta-Analysis

BACKGROUND Obesity is associated with increasing morbidity and mortality in many prevalent diseases, especially lumbar degenerative disease. The relationship between minimally invasive surgery (MIS) of the spine and perioperative adverse events in obese patients with lumbar degenerative disease has not been well evaluated. METHODS We conducted a systematic review and meta-analysis to identify relevant studies involving obese patients with spine MIS in electronic databases up to June 2017, including Web of Science, Embase, PubMed, the Cochrane Controlled Trials Register, and the Cochrane Library. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system, and Cochrane Handbook were applied to assess the quality of the results published in all included studies. RESULTS No significant difference was found in postoperative complications between obese and nonobese patients, according to the Oswestry Disability Index, and visual analog scale. However, there were significant differences between the 2 groups in surgery time, blood loss, and length of hospital stay. CONCLUSIONS There does not seem to be an increased risk of developing perioperative complications in obese patients undergoing spine MIS. Spine MIS was a safe and effective technique for obese patients. However, according to our pooled data, longer surgery time was observed in obese patients.