To review the advance in the experimental studies and evaluate the potential therapeutic appl ication of the growth differentiation factor 5(GDF-5) and osteogenic protein 1 (OP-1) in intervertebral disc degeneration.Methods Relevant l iterature at home and abroad publ ished in recent years was searched and analyzedcomprehensively. Results The growth factor was one of the most potential proteins in curing the intervertebral discdegeneration. In vitro, exogenous GDF-5 or OP-1 increased the deoxyribonucleic acid and proteoglycan contents ofboth nucleus pulposus and annlus fibrosis cells types significantly. GDF-5 at 200 ng/mL or OP-1 significantly stimulatedproteoglycan synthesis and collagen synthesis. In vivo, the injection of GDF-5(100 μg) or OP-1(100 μg in 10 μL 5% lactose) resulted in a restoration of disc height, improvement of magnetic resonance imaging scores, and histologic grading scores had statistical significance. Conclusion A single injection of GDF-5 or OP-1 has a reparative capacity on intervertebral discs, presumably based on its effect to stimulate matrix metabol ism of intervertebral disc cells and enhance extracellular matrix production. A single injection of exogenous GDF-5 or OP-1 in the degenerated disc shows a good prospect.
Objective To evaluate the cell biological features and the effect of transplantation of transforming growth factor β3 (TGF-β3) gene-modified nucleus pulposus (NP) cells on the degeneration of lumbar intervertebral discs in vitro. Methods NP cells at passage 2 were infected by recombinant adenovirus carrying TGF-β3 (Ad-TGF-β3) gene (Ad-TGF-β3 group), and then the cell biological features were observed by cell vital ity assay, the expression of the TGF-β3 protein was determined by Western blot, the expression of collagen type II in logarithmic growth phase was determined by immunocytochemistry. The cells with adenovirus-transfected (Adv group) and the un-transfected cells (blank group) were used as controls. The model of lumbar disc degeneration was establ ished by needl ing L3, 4, L4, 5, and L5, 6 in 30 New Zealand rabbits (weighing 3.2-3.5 kg, male or female). Then Ad-TGF-β3-transfected rabbit degenerative nucleus pulposus cells (100 μL, 1 × 105/ mL, group A, n=12), no gene-modified nucleus pulposus cells (100 μL, 1 × 105/mL, group B, n=12), and phosphatebuffered sal ine (PBS, 100 μL, group C, n=6) were injected into degenerative lumbar intervertebral discs, respectively. L3, 4, L4, 5, and L5, 6 disc were harvested from the rabbits (4 in groups A and B, 2 in group C) at 6, 10, and 14 weeks respectively to perform histological observation and detect the expression of collagen type II and proteoglycan by RT-PCR. Results The viabil ity of nucleus pulposus cells was obviously improved after transfected by recombinant Ad-TGF-β3 gene. At 3, 7, and 14 days after transfected, TGF-β3 expression gradually increased in nucleus pulposus cells. The positive staining of collagen type II was seen in Ad-TGF-β3 group, and the positive rate was significantly higher than that of Adv group and blank group (P lt; 0.05). The disc degeneration in group A was sl ighter than that in groups B and C. The expressions of collagen type II mRNA and proteoglycan mRNA in group A were significantly higher than those in groups B and C at 6, 10, and 14 weeks (P lt; 0.05). Conclusion TGF-β3 can improve the biological activity of NP cells and promote the biosynthesis of collagen type II and proteoglycan in intervertebral discs, alleviate the degeneration of intervertebral discs after transplantation.
ObjectiveTo compare the effectiveness of decompression and short fusion or long fusion for degenerative scoliosis (DS) with a Cobb angle of 20-40° combined with spinal stenosis.MethodsThe clinical data of 50 patients with DS who were treated with decompression combined with short fusion or long fusion between January 2015 and May 2017 were retrospectively analysed. Patients were divided into long fusion group (fixed segments>3, 23 cases) and short fusion group (fixed segments≤3, 27 cases). There was no significant difference in gender, age, disease duration, and preoperative visual analogue scale (VAS) score of leg pain, Oswestry disability index (ODI), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), pelvic incidence (PI), pelvic title (PT), and sacral slope (SS) between the two groups (P>0.05); however, the VAS score of low back pain, Cobb angle, and sagittal vertical axis (SVA) in long fusion group were significantly higher than those in short fusion group (P<0.05), and the lumbar lordosis (LL) was significantly lower than that in short fusion group (t=2.427, P=0.019). The operation time, intraoperative blood loss, fluoroscopy times, hospital stay, and complications were recorded and compared. The VAS scores of low back pain and leg pain and ODI score were used to evaluate the clinical outcomes before operation and at last follow-up. X-ray films of the whole spine in standard standing position were taken before operation, at 6 months after operation, and at last follow-up, and the spino-pelvic parameters were measured.ResultsThe operation time, intraoperative blood loss, and fluoroscopy times in the short fusion group were significantly less than those in the long fusion group (P<0.05); there was no significant difference in hospital stay between the two groups (t=0.933, P=0.355). The patients were followed up 12-46 months with an average of 22.3 months. At last follow-up, the VAS scores of low back pain and leg pain and ODI score significantly improved when compared with those before operation (P<0.05). Except for the improvement of VAS score of low back pain (t=8.332, P=0.000), the differences of the improvements of the other scores between the two groups were not significant (P>0.05). The Cobb angle, SVA, TLK, and PT significantly decreased, while SS and LL significantly increased in the long fusion group (P<0.05), while the Cobb angle and PT significantly decreased and SS significantly increased in the short fusion group at last follow-up (P<0.05). There was no significant difference in spino-pelvic parameters between the two groups at 6 months after operation and at last follow-up (P>0.05). The improvements of Cobb angle, SVA, LL, PT, and SS in the long fusion group were significantly higher than those in the short fusion group at last follow-up (P<0.05). There was no perioperative death in both groups. The incidence of complications in the long fusion group was 34.8% (8/23), which was significantly higher than that in the short fusion group [11.1% (3/27)] (χ2=4.056, P=0.034).ConclusionThe DS patients with the Cobb angle of 20-40°can achieve satisfactory clinical outcomes and improve the spino-pelvic parameters by choosing appropriate fixation levels. Short fusion has less surgical trauma and fewer complications, whereas long fusion has more advantages in enhancing spino-pelvic parameters and relieving low back pain.
Objective To develop a modified short time inversion recovery (STIR) sequence grading system for lumbar intervertebral disc degeneration based on MRI STIR sequences, and to test the validity and reproducibility of this grading system. Methods A modified 8-level grading system for lumbar intervertebral disc degeneration based on routine sagittal STIR sequences and modified Pfirrmann grading system was developed. Between April 2011 and February 2012, 60 patients with different degrees of lumbar intervertebral disc degeneration were selected as objects of study, including 32 males and 28 females with an average of 50 years (range, 17-85 years). T2 weighted and STIR sequence images were obtained from the lumbar discs of L1, 2-L5, S1 of each object (total, 300 discs). All examinations were analyzed independently by 3 observers and a consensus readout was performed after all data collected. The validity and reproducibility were analyzed by calculating consistent rate and Kappa value. Results According to the grading system, there were 0 grade 1, 83 (27.7%) grade 2, 87 (29.0%) grade 3, 66 (22.0%) grade 4, 31 (10.3%) grade 5, 15 (5.0%) grade 6, 12 (4.0%) grade 7, and 6 (2.0%) grade 8. Intra-observer consistency was b (Kappa value range, 0.822-0.952), and inter-observer consistency was high to b (Kappa value range, 0.749-0.843). According to the consensus analysis, the total consistent rate was 82.7%-92.7% (mean, 85.6%). A difference of one grade occurred in 13.9% and a difference of two or more grades in 0.5% of all the cases. Conclusion Disc degeneration can be graded by using modified STIR sequence grading system, which can improve the accuracy of grading different degrees of lumbar intervertebral disc degeneration.
ObjectiveTo investigate the expressions of cartilage degenerative related genes in meniscus, and to evaluate the potential effect of meniscal damage on cartilage degeneration, and to analyze the relationship between microRNAs (miRNAs) expression and cartilage degeneration. MethodsMeniscal tissue was collected from 5 patients undergoing partial meniscectomy between September 2012 and October 2013 (experimental group), and normally meniscal tissue without tearing from amputees was used as controls (control group). Pathological changes of menisci were observed; and real-time fluorescent quatitative PCR was performed to examine the relative expression levels of cartilage degenerative related genes and miRNAs:Aggrecan (ACAN), type X collagen (COL10A1), matrix metalloproteinases 13 (MMP-13), CCAAT enhancer binding protein β (CEBP-β), a disintegrin and metalloproteinase with thrombospondinmotif 5 (ADAMTS-5), miR-193b, miR-92a, and miR-455-3p in meniscus. ResultsThere were varying degrees of degenerative pathological changes in torn meniscus of experimental group. Compared with normal meniscus of control group, the expression of ACAN was decreased, while the expressions of COL10A1, CEBP-β, ADAMTS-5, and MMP-13 were increased in torn meniscus of experimental group; and significant difference was found (P<0.05) except ACAN and MMP-13 (P>0.05). The expressions of miR-92a, miR-455-3p, and miR-193b in torn meniscus of experimental group were significantly higher than those in normal meniscus of control group (P<0.05). ConclusionMeniscal tissue has the intrinsic tendency of degeration after meniscus tear. The torn meniscus has greater stimulative impact on cartilage degeneration than normally morphological meniscus without tearing. The cartilage degenerative related miRNAs, including miR-193b, miR-92a, and miR-455-3p may contribute to the up-regulation of osteoarthritis.
ObjectiveTo investigate the correlation between CT value and Cage subsidence in patients with lumbar degenerative disease treated with stand-alone oblique lumbar interbody fusion (OLIF). MethodsThe clinical data of 35 patients with lumbar degenerative diseases treated with stand-alone OLIF between February 2016 and October 2018 were retrospectively analyzed. There were 15 males and 20 females; the age ranged from 29 to 81 years, with an average of 58.4 years. There were 39 operative segments, including 32 cases of single-segment, 2 cases of double-segment, and 1 case of three-segment. Preoperative lumbar CT was used to measure the CT values of the axial position of L1 vertebral body, the axial and sagittal positions of L1-4 vertebral body, surgical segment, and the axial position of upper and lower vertebral bodies as the bone mineral density index, and the lowest T value was recorded by dual-energy X-ray absorptiometry. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores were recorded before operation and at last follow-up. At last follow-up, the lumbar interbody fusion was evaluated by X-ray films of the lumbar spine and dynamic position; the lumbar lateral X-ray film was used to measure the subsidence of the Cage, and the patients were divided into subsidence group and nonsubsidence group. The univariate analysis on age, gender, body mass index, lowest T value, CT value of vertebral body, disease type, and surgical segment was performed to initially screen the influencing factors of Cage subsidence; further the logistic regression for multi-factor analysis was used to screen fusion independent risk factors for Cage subsidence. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the CT value and the lowest T value to predict the Cage subsidence. Spearman correlation analysis was used to determine the correlation between Cage subsidence and clinical results. Results All the 35 patients were followed up 27-58 months, with an average of 38.7 months. At last follow-up, the VAS and ODI scores were significantly decreased when compared with preoperative scores (t=32.850, P=0.000; t=31.731, P=0.000). No recurrent lower extremity radiculopathy occurred and no patient required revision surgery. Twenty-seven cases (77.1%) had no Cage subsidence (nonsubsidence group); 8 cases (22.9%) had at least radiographic evidence of Cage subsidence, the average distance of Cage subsidence was 2.2 mm (range, 1.1-4.2 mm) (subsidence group). At last follow-up, there was 1 case of fusion failure both in the subsidence group and the nonsubsidence group, there was no significant difference in the interbody fusion rate (96.3% vs. 87.5%) between two groups (P=0.410). Univariate analysis showed that the CT value of vertebral body (L1 axial position, L1-4 axial and sagittal positions, surgical segment, and upper and lower vertebral bodies axial positions) and the lowest T value were the influencing factors of Cage subsidence (P<0.05). According to ROC curve analysis, compared with AUC of the lowest T value [0.738, 95%CI (0.540, 0.936)], the AUC of the L1-4 axis CT value was 0.850 [95%CI (0.715, 0.984)], which could more effectively predict Cage subsidence. Multivariate analysis showed that the CT value of L1-4 axis was an independent risk factor for Cage subsidence (P<0.05). Conclusion The CT value measurement of the vertebral body based on lumbar spine CT before stand-alone OLIF can predict the Cage subsidence. Patients with low CT values of the lumbar spine have a higher risk of Cage subsidence. However, the Cage subsidence do not lead to adverse clinical results.
Objective To review the research advances in animal models of human disc degeneration. Methods The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Results Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Conclusion Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.
Objective To compare the effectiveness and radiological changes of posterior decompression combined with Coflex interspinous dynamic reconstruction or lumbar 360° fusion for degenerative lumbar spinal disorders at L4, 5. MethodsBetween October 2008 and November 2010, a comparative study was carried out on patients with degenerative lumbar spinal disorders at L4, 5. In group A, 29 patients underwent posterior decompression combined with Coflex interspinous dynamic reconstruction; there were 20 males and 9 females with an average age of 45.1 years (range, 21-67 years); and the disease duration was 2 months to 4 years. In group B, 31 patients underwent posterior decompression combined with lumbar 360° fusion treatment; there were 16 males and 15 females with an average age of 56.2 years (range, 32-86 years); and the disease duration was 3 months to 6 years. Except the age, there was no significant difference in gender, disease duration, and etiology etc. between 2 groups (P gt; 0.05). The results were assessed by Japanese Orthopaedic Association (JOA), visual analogue scale (VAS) scores, and Oswestry disabil ity index (ODI). The range of motion (ROM) and intervertebral height of affected and adjacent segments, and the ROM of lumbar were measured before operation and last follow-up. Results Significant differences were found in the operative time and blood loss between 2 groups (P lt; 0.05). Intraoperative dural tear occurred in 1 case of group B, spinal canal venous plexus hemorrhage in 1 case of group B, and postoperative cerebrospinal fluid leakage in 2 cases of group A and B respectively, showing no significant difference (χ2=0.119, P =0.731). The follow-up was 12-21 months in group A and was 12-23 months in group B. At the last follow-up, the JOA, VAS scores, and ODI of groups A and B were significantly improvedwhen compared with the preoperative values (P lt; 0.05). The VAS score of group A was significantly higher than that of group B (P lt; 0.05). There was no significant difference in the intervertebral height of L4, 5 and L5, S1 of groups A and B between pre- and post-operation (P gt; 0.05). In group B, the intervertebral height of L3, 4 was significantly reduced (P lt; 0.05) compared with the preoperative one. There was no significant difference in the ROM of L5, S1 and ROM of lumbar in groups A and B between preand post-operation (P gt; 0.05). At last follow-up, the ROM of L4, 5 was significantly reduced in group A (P lt; 0.05), and the ROM of L3, 4 was significantly increased in group B (P lt; 0.05). Except significant differences in the intervertebral height and ROM of L3, 4 between 2 groups (P lt; 0.05), no significant difference was found in other parameters (P gt; 0.05). Conclusion Posterior decompression combined with Coflex interspinous dynamic reconstruction has the same effectiveness as lumbar 360° fusion in treating degenerative lumbar spinal disorders at L4, 5, but the former has a protective effect on the adjacent segments of fusion and is recommended for initial treatment of young adults and the elderly and frail patients with recurrent.
Objective To analyze the cl inical effects of modified transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degenerative disease. Methods From October 2003 to December 2006, 33 patients with lumbar degenerative disease (L3-S1) were treated by modified TLIF. There were 14 males and 19 females with an average age of 52.2 years(33 to 70 years). The median disease course was 1.8 years (4 months to 15 years). A total of 42 levels were fused, including 24 cases of single level and 9 cases of double levels. The results of preoperative diagnosis were lumbar degenerative spondylol isthesis with stenosis (8 cases), isthmic spondylol isthesis (5 cases), degenerative lumbar stenosis (16 cases), huge herniated disc with segmental instabil ity (3 cases) and failed back surgery syndrome (1 case). During the modified TLIF procedure, total inferior facet process and inner half summit of superior facet process of TLIF side were resected to make the posterior wall of foramen opened partly. After the bone graft (3 to 5 mL) was placed into the interbody space, a single rectangle Cage was inserted obl iquely from 30° to 40° toward the midl ine. Combined with pedicle screw instrumentation, TLIF was accompl ished. Middle canal and opposite side nerve root decompression were performed simultaneously when necessary. Results Intraoperative dura mater rupture, postoperative cerebral spinal fluid leakage, deep wound infection and transient nerve root stimulation occurredin 1 case respectively, and were all recovered after treatment. No patients had permanent neurologic deficit or aggravation. All patients were followed up for 20 to 58 months (mean 27.2 months). At the follow-up after 1 year postoperatively, all the operated segments achieved fusion standard and no broken screw or Cage dislocation occurred. All 13 cases of spondylol isthesis were reduced thoroughly and maintained satisfactorily. Nineteen patients remained sl ight chronic back pain. There was significant difference (P lt; 0.05) in JOA score between preoperation (14.9 ± 5.1) and postoperation (25.9 ± 3.0). The rate of cl inical improvement was 80.5% (excellent in 24 cases, good in 7 cases, and fair in 2 cases). Conclusion The modified TLIF carries out the less invasive principles in opening operations, simpl ifies the manipulation and expands the indication of TLIF to some extent, and the cl inical results for the treatment of lumbar degenerative disease is satisfactory.
Objective To investigate the effect of resveratrol (RES) on inflammation-induced cartilage endplate (CEP) degeneration, and its regulatory mechanism on high mobility group box-1 protein (HMGB1) signaling pathway. Methods The intervertebral CEP cells of Sprague Dawley (SD) rats aged 3 weeks were extracted and identified by toluidine blue staining and immunofluorescence staining of rabbit anti-rat collagen type Ⅱ. The cell counting kit 8 (CCK-8) method was used to screen the optimal concentration of RES on intervertebral CEP cells. Gene chip analysis was used to determine the target of RES on intervertebral CEP cells. Interleukin 1β (IL-1β) was used to construct the intervertebral CEP cell degeneration model caused by inflammation and the 7-8-week-old SD rat intervertebral disc degeneration model, and pcDNA3.1-HMGB1 (pcDNA3.1) was used as the control of RES effect. Flow cytometry and TUNEL staining were used to detect the apoptotic rate of intervertebral CEP cells and rat intervertebral disc tissue cells, respectively. ELISA kit was used to detect the content of interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) in the cell supernatant and rat serum. Western blot was used to detect the expressions of HMGB1, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (p-ERK), B cell lymphoma/leukemia 2 gene (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsThe extracted cells were identified as rat intervertebral CEP cells. CCK-8 method screened out the highest activity of intervertebral CEP cells treated with 30 μmol/L RES. The gene chip analysis confirmed that the HMGB1-ERK signal was the target of RES. Both cell experiments and animal experiments showed that RES treatment can significantly down-regulate the apoptosis rate of intervertebral CEP cells, inhibit the release of TNF-α, and increase the content of IL-10; and down-regulate the expressions of HMGB1, p-ERK, and Bax, and increase Bcl-2; and pcDNA3.1 could partially reverse these effects of RES, and the differences were all significant (P<0.05). ConclusionRES can significantly inhibit the apoptosis of intervertebral CEP cells induced by inflammation, which is related to inhibiting the expression of HMGB1.