Jiwei Tian

IL-1β promotes ADAMTS enzyme-mediated aggrecan degradation through NF-κB in human intervertebral disc

BackgroundThe purpose of this study is to investigate IL-1β regulation of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS-5) expression through nuclear factor kappa B (NF-κB) in human nucleus pulposus (NP) cells.MethodsqRT-PCR and Western blot were used to measure ADAMTS expression. Transfections and gene silencing were used to determine the role of NF-κB on cytokine-mediated ADAMTS expression and its role in aggrecan degradation.ResultsIL-1β increased ADAMTS expression in NP cells. Treatment with NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS expression. Silencing of p65 confirmed their role in IL-1β-dependent ADAMTS-4 and ADAMTS-5 expression and aggrecan degradation.ConclusionsBy controlling the activation of NF-κB signaling, IL-1β modulates the expression of ADAMTS in NP cells. To our knowledge, this is the first study that shows the contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells.

Combination of bone marrow concentrate and PGA scaffolds enhance bone marrow stimulation in rabbit articular cartilage repair.

Bone marrow stimulation (BMS) has been regarded as a first-line procedure for the repair of articular cartilage. However, cartilage repair using BMS alone has so far not been ideal because cell homing to the required area has not been sufficient. The aim of this study was to investigate the feasibility of autologous bone marrow concentrate transplantation for the repair of large, full-thickness cartilage defects. Thirty rabbits were divided into five groups: untreated (control); BMS only (BMS); BMS followed by PGA implantation (PGA); BMS followed by a combination of PGA and autologous bone marrow concentrate (BMC); and BMS together with a composite of PGA and cultured bone marrow stem cells (BME). The animals were sacrificed at week 8 after operation, and HE staining, toluidine blue staining and immunohistochemistry were used to assess the repair of defects. The results showed that improved repair, including more newly formed cartilage tissue and hyaline cartilage-specific extracellular matrix, was observed in BMC group relative to the first three groups, in addition similar results were found between BMC and BME groups, however it took longer time for in vitro cell expansion in the BME group. This study demonstrates that the transplantation of autologous bone marrow concentrate is an easy, safe and potentially viable method to contribute to articular cartilage repair.

The Changes in the Expression of NF-KB in a Degenerative Human Intervertebral Disc model

We aim at determining the changes in the expression of NF-kB signaling pathway in degenerative intervertebral discs. We collected normal and degenerated intervertebral discs tissues. The normal and degenerated cells were cultivated and their histopathology and immunofluoresence studies were used to observe the position of NF-kB p65 in the cell. We also treated the nucleus pulposus cells with inflammatory factors and inhibitors. Western blot was used to analyze the expression of different proteins. Real time fluorescence-based quantitative PCR was used for observation of NF-kB regulation of change in gene expression. Immunofluorescence showed that in the non-degenerative group the p65 was found in the cytoplasm of the nucleus pulposus cell while in the degenerated cell group the p65 protein was found in the nucleus of the cell. The expression of p65 increased with increase in the degree of degenerative change of the nucleus pulposus cell. RT-PCR showed that the expression of matrix metalloproteinases, aggrecanases and IL-6 was higher in the degenerative group. The amount of aggrecan and type II collagen was significantly decreased in the degenerative group. IL-1β was able to upregulate the activation of NF-kB and the expression of MMP-13 and ADAMTS-4 was also significantly increased. The effect of these proteins can be inhibited by the NF-kB inhibitor, BAY11-7082. The activation of the NK-kB signaling pathway in a degenerative intervertebral disc is gradually increased, regulating the over-expression of matrix-degrading enzymes. It plays an important role in the degradation of extracellular matrix.

Early clinical effects of the Dynesys system plus transfacet decompression through the Wiltse approach for the treatment of lumbar degenerative diseases

Background This study investigated early clinical effects of Dynesys system plus transfacet decompression through the Wiltse approach in treating lumbar degenerative diseases. Material/Methods 37 patients with lumbar degenerative disease were treated with the Dynesys system plus transfacet decompression through the Wiltse approach. Results Results showed that all patients healed from surgery without severe complications. The average follow-up time was 20 months (9–36 months). Visual Analogue Scale and Oswestry Disability Index scores decreased significantly after surgery and at the final follow-up. There was a significant difference in the height of the intervertebral space and intervertebral range of motion (ROM) at the stabilized segment, but no significant changes were seen at the adjacent segments. X-ray scans showed no instability, internal fixation loosening, breakage, or distortion in the follow-up. Conclusions The Dynesys system plus transfacet decompression through the Wiltse approach is a therapeutic option for mild lumbar degenerative disease. This method can retain the structure of the lumbar posterior complex and the motion of the fixed segment, reduce the incidence of low back pain, and decompress the nerve root.

Posterior pedicle screw fixation for complex atlantoaxial fractures with atlanto-dental interval of ≥5 mm or C2-C3 angulation of ≥11°

ObjectivePrevious studies have demonstrated that the posterior pedicle screw fixation is an effective and safe method to treat atlantoaxial fractures. However, no report focuses on only the complex atlantoaxial fractures with atlanto-dental interval (ADI) of ≥5 mm or C2-C3 angulation of ≥11°.MethodsThis study was to retrospectively evaluate the outcome of 15 patients (six females and nine males; age, 27–55 years) who underwent posterior pedicle screw fixation for the above complex atlantoaxial fractures between July 2006 and March 2011. Fracture combinations included three Jefferson-type II odontoid, four anterior ring-type II odontoid, two posterior ring-type II odontoid, one lateral mass-type II odontoid, one Jefferson-hangmans fracture, three anterior ring-hangmans fracture, and one lateral mass-hangmans fracture. Fracture healing and bone fusion were determined on X-ray scan. Upper limbs, lower limbs, and sphincter functions were assessed using the Japanese Orthopaedic Association (JOA) score. The Frankel grading system was used to determine the neurological situation.ResultsThe mean operative time, blood loss, and hospital stays were 108.9 ± 25.8 min, 508.0 ± 209.6 ml, and 13.3 ± 2.0 days. Fracture healing and graft fusion were obtained in all patients within 9 months. The ADI or C2-C3 angulation was reduced to ≤5 mm or ≤11°. The JOA score was significantly improved from 7.27 ± 1.10 preoperatively to 15.7 ± 2.1 postoperatively (P <0.001), with 88.1 ± 18.3% recovery rate and 93.3% excellent and good rate. The neurological situation was improved in all patients by at least 1 grade in the Frankel scale. After a mean of 36.5 months of follow-up (range, 18 to 58 months), no operative complications (spinal cord injury, vertebral artery injury, or cerebrospinal fluid leakage) were observed.ConclusionPosterior pedicle screw fixation is a reliable, effective, and minimally invasive procedure for patients suffering from complex atlantoaxial fractures.

Investigation of candidate genes for osteoarthritis based on gene expression profiles.

Objective To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. Methods Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein–protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules. Results In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs were involved in inflammatory response, while down-regulated DEGs were involved in cell cycle. PPI network with 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle. Conclusion The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for gene therapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle and cytokine–cytokine receptor interaction pathway.

Outcomes of surgery for unstable odontoid fractures combined with instability of adjacent segments

BackgroundAt present, traumatic atlantoaxial dislocation or C2-3 instability complicating odontoid fractures remains rarely reported. The aim of this study was to further investigate the surgical treatment strategies and curative effects for odontoid fractures combined with instability of adjacent segments.MethodsThis is a retrospective study of 12 patients (5 females and 7 males; age, 21-65 years) who underwent internal fixation for odontoid fractures (type II and shallow type III) and atlantoaxial instability in 6 cases, C2-3 instability in 4 cases, simultaneous C1-2 and C2-3 instability in 2 cases between January 2005 and June 2012. Accordingly, individualized surgeries were performed. Fracture healing and bone fusion were determined on X-ray scan. Upper limbs, lower limbs and sphincter functions were assessed using the Japanese Orthopaedic Association (JOA) score. Frankel grading system was used for the evaluation of neurological situation.ResultsMean follow-up time of all 12 cases was 16.4 months (range, 12 to 48 months). Odontoid fracture healing was obtained in all patients within 9 months, and graft fusion was achieved within 6 months. JOA score was significantly improved from 6.3 ± 3.1 preoperatively to 11.1 ± 4.6 at 12 months after operation (P = 0.007), with 50.5 ± 25.7% recovery rate and 66.7% excellent and good rate. Except one patient still had Frankel grade B neurological injury at 12 months after surgery, the other patients improved their neurological situation (at 1 grade in Frankel scale). One patient developed wound fat liquefaction which resolved by changing the dressing. Cerebrospinal fluid leakage occurred in three patients, which resolved after the continuous drainage for 2 days.ConclusionsAccording to the characteristics of odontoid fractures, the individualized operative procedure should be performed, resulting in high fracture healing rate, function recovery rate, and less, transient complications.

New progress in adjacent segment degeneration/disease

Adjacent segment degeneration/disease (ASD) has been generally accepted as a long‐term complication after spinal surgery. Although the incidence of ASD is not very high, it is gradually recognized to be a very important factor in evaluation of the long‐term effect of spinal fusion. There are many views concerning pathogenic factors and ways of prevention and treatment. The authors review and discuss the current research and this article will describe recent advances in ASD.

Surgical treatment of complex axis fractures with adjacent segment instability.

This study investigates the clinical and radiographic characteristics of complex axis fractures with adjacent segment instability and describes the outcome of surgical treatment. Twenty-one patients (14 male, seven female; mean age=34 years) with complex axis fractures and adjacent segment instability who were treated between August 2003 and June 2009 were retrospectively reviewed. Treatment selection was based on fracture type and stability of the upper cervical segments. All patients were immobilized with a hard collar for three months after surgery. The mean follow-up period was 12 months (range=6-36 months). No intraoperative surgery-related complications were observed and fusion was achieved in all patients. The outcome was excellent for 17 patients, good for two patients, fair for one patient, and poor for one patient. The upper cervical segments that can become unstable due to complex axis fractures include the atlantoaxial and C2-3 joints. Recommended surgical treatments produce good results.

Psammomatous melanotic schwannoma with cystic changes from old hemorrhages in the cervical spinal canal: a case report

Psammomatous melanotic schwannoma (PMS) represents a rare type of schwannoma; its occurrence in the spinal canal is even rarer. In the present study, we report a case of pathologically confirmed PMS with cystic changes from old hemorrhages in the cervical spinal canal. The patient underwent surgical resection of the tumor with postoperative radiotherapy, and had a smooth recovery. Follow-up X-rays and MRI at 16 months after the operation revealed no evidence of tumor recurrence.