Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNA molecules, which regulate the gene expression at the post-transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease.
Apoptosis ; Extracellular Matrix ; pathology ; Gene Expression ; Gene Expression Profiling ; Humans ; Intervertebral Disc Degeneration ; genetics ; pathology ; MicroRNAs ; genetics

Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion.
Humans ; Intervertebral Disc Degeneration ; Natural History ; Pathology* ; Reoperation ; Risk Factors ; Smoke ; Smoking ; Spinal Fusion ; Spine ; Sports ; Standard of Care ; Total Disc Replacement ; Viperidae

OBJECTIVE: To evaluate T2 relaxation time change using axial T2 mapping in a rabbit degenerated disc model and determine the most correlated variable with histologic score among T2 relaxation time, disc height index, and Pfirrmann grade. MATERIALS AND METHODS: Degenerated disc model was made in 4 lumbar discs of 11 rabbits (n = 44) by percutaneous annular puncture with various severities of an injury. Lumbar spine lateral radiograph, MR T2 sagittal scan and MR axial T2 mapping were obtained at baseline and 2 weeks and 4 weeks after the injury in 7 rabbits and at baseline and 2 weeks, 4 weeks, and 6 weeks after the injury in 4 rabbits. Generalized estimating equations were used for a longitudinal analysis of changes in T2 relaxation time in degenerated disc model. T2 relaxation time, disc height index and Pfirrmann grade were correlated with the histologic scoring of disc degeneration using Spearman's rho test. RESULTS: There was a significant difference in T2 relaxation time between uninjured and injured discs after annular puncture. Progressive decrease in T2 relaxation time was observed in injured discs throughout the study period. Lower T2 relaxation time was observed in the more severely injured discs. T2 relaxation time showed the strongest inverse correlation with the histologic score among the variables investigated (r = -0.811, p < 0.001). CONCLUSION: T2 relaxation time measured with axial T2 mapping in degenerated discs is a potential method to assess disc degeneration.
Animals ; Disease Models, Animal ; Intervertebral Disc/injuries/*pathology ; Intervertebral Disc Degeneration/*pathology ; Lumbar Vertebrae/*pathology ; Magnetic Resonance Imaging/*methods ; Male ; Punctures ; Rabbits

OBJECTIVES: To study the characteristics of the relationship between injury and disease in forensic identification cases of cervical trauma with cervical vertebra degeneration, and to explore the problems about how to identify the participation rates of injury and disease using the clinical information, forensic examination and imaging examination. METHODS: Seventeen forensic identification cases of cervical trauma with cervical vertebra degeneration were collected. The age distributions, injury formations, injury severities and imaging findings of these cases were analyzed and the relationship between injury and disease was evaluated comprehensively. RESULTS: Middle-aged and elderly were common in 17 cases and every case was involved with intervertebral disc herniation. The main reasons of injuries were hyperextension. The degree of injury severity and vertebra degeneration were graded according to the imaging findings. The participation rates of injury and disease were also calculated comprehensively. CONCLUSIONS The forensic identification cases of cervical trauma with cervical vertebra degeneration should be evaluated with clinical information, forensic examination and imaging finding.
Adult ; Age Distribution ; Aged ; Cervical Vertebrae/pathology* ; Humans ; Intervertebral Disc Degeneration/pathology* ; Intervertebral Disc Displacement/pathology* ; Middle Aged

OBJECTIVETo explore the clinical effects of Dynesys system for the treatment of multiple segment lumbar degenerative disease.

METHODSA total of 28 patients with lumbar degenerative disc disease treated with Dynesys system from December 2008 to May 2011 were retrospectively reviewed. There were 16 males and 12 females, aged from 27 to 75 years old with an average of 49.1 years. Thirteen patients with multiple segmental lumbar intervertebral disc protrusion, including L3-L5 in 7 cases, L2-L4 in 1 case and L4-S1 in 5 cases. Fifteen patients with multiple segmental lumbar spinal stenosis, including L3-L5 in 10 cases, L4-L5 in 4 cases and L2-S1 in 1 case. The symptoms of lumbago and (or) intermittent claudication in all patients were treated with conservative treatments for more than 6 months and these methods did not work. Visual analogue scale (VAS) was used to analyze the lumbar and leg pain, imaging data were used to measure the intervertebral space height and intervertebral motion of fixed segment and upper adjacent segment, Oswestry Disability Index (ODI) was used to evaluate the clinical effect.

RESULTSAll operations were successful and the patients were followed up from 38 to 65 months with an average 50.6 months. At final follow-up, ODI and VAS of the low back pain and leg pain were (25.10±6.52)%, (1.25±0.70) points and (1.29±0.89) points, respectively and were decreased compared with preoperative (P<0.05). Postoperative intervertebral space heights were increased and intervertebral motions were decreased in fixed segment compared with preoperative (P<0.05). There were no significant differences in intervertebral space heights and intervertebral motions of upper adjacent segment between preoperative and postoperative (P>0.05).

CONCLUSIONDynesys system may obtain long-term clinical curative effect in treating multiple lumbar degenerative disease. It can partially preserve the intervertebral motions of the fixed segments, have little effect on adjacent segments. The long-term clinical effect of Dynesys still need longer time follow-up observation.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Degeneration ; pathology ; surgery ; Joint Instability ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Visual Analog Scale

A geometrical model of L4-L5 lumbar segment was constructed using a three-dimensional graphics software. Four conditions of the degenerated discs, i. e. light degeneration, moderate degeneration, severe degeneration and complete excision degeneration, were simulated with loading situations using finite element method under the condition of appropriate computational accuracy. By applying a vertical load of 378.93 N on L4 vertebral plate, stress nephograms on joint isthmus under four different working conditions were obtained. The results showed that the contacted area of facet joint was influenced by the degree of intervertebral disc degeneration level, which influenced the mises stress on joint isthmus. It was proved that joint isthmus was the important pressure-proof structure of the back of lumbar vertebra, and the stress values and distribution were related to structural stiffness of the back of lumbar vertebra as well as the contact area of facet joint. The conclusion could be the theoretical reference for the analysis of spinal biomechanics and artificial disc replacement as well.
Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Intervertebral Disc ; pathology ; Intervertebral Disc Degeneration ; Lumbar Vertebrae ; physiopathology ; Models, Anatomic ; Pressure ; Zygapophyseal Joint

PURPOSE: To investigate the molecular responses of various genes and proteins related to disc degeneration upon treatment with cytokines that affect disc-cell proliferation and phenotype in living human intervertebral discs (IVDs). Responsiveness to these cytokines according to the degree of disc degeneration was also evaluated. MATERIALS AND METHODS: The disc specimens were classified into two groups: group 1 (6 patients) showed mild degeneration of IVDs and group 2 (6 patients) exhibited severe degeneration of IVDs. Gene expression was analyzed after treatment with four cytokines: recombinant human bone morphogenic protein (rhBMP-2), transforming growth factor-beta (TGF-beta), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). Molecular responses were assessed after exposure of cells from the IVD specimens to these cytokines via real-time polymerase chain reaction and immunofluorescence staining. RESULTS: mRNA gene expression was significantly greater for aggrecan, type I collagen, type II collagen, alkaline phosphatase, osteocalcin, and Sox9 in group 1 than mRNA gene expression in group 2, when the samples were not treated with cytokines. Analysis of mRNA levels for these molecules after morphogen treatment revealed significant increases in both groups, which were much higher in group 1 than in group 2. The average number of IVD cells that were immunofluorescence stained positive for alkaline phosphatase increased after treatment with rhBMP-2 and TGF-beta in group 1. CONCLUSION: The biologic responsiveness to treatment of rhBMP-2, TGF-beta, TNF-alpha, and IL-1beta in the degenerative living human IVD can be different according to the degree of degeneration of the IVD.
Adult ; Aggrecans/genetics/metabolism ; Alkaline Phosphatase/genetics/metabolism ; Biological Products/pharmacology/*therapeutic use ; Bone Morphogenetic Protein 2/pharmacology/therapeutic use ; Collagen Type I/genetics/metabolism ; Collagen Type II/genetics/metabolism ; Cytokines/*pharmacology/*therapeutic use ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation/drug effects ; Humans ; Interleukin-1/pharmacology/therapeutic use ; Intervertebral Disc/*drug effects/*pathology ; Intervertebral Disc Degeneration/*drug therapy/genetics/*pathology ; Male ; Middle Aged ; Osteocalcin/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Recombinant Proteins/pharmacology/therapeutic use ; SOX9 Transcription Factor/genetics/metabolism ; Transforming Growth Factor beta/pharmacology/therapeutic use ; Tumor Necrosis Factor-alpha/pharmacology

OBJECTIVETo assess the correlation between vertebral body deformity and degeneration of the adjacent intervertebral discs in patients with old thoracolumbar compression fractures.

METHODSSeventy-one patients who had been conservatively treated after single segment thoracolumbar compression fractures between April, 2011 and May, 2014 were enrolled in this study. Both radiographic and magnetic resonance (MR) images of the thoracolumbar segment were obtained. The involved vertebral body deformity was rated on radiography according to the Genant criterion, and the degeneration of the adjacent cephalic and caudal discs was assessed on MR images using the Oner and Pfirrmann classification schemes, respectively. The relationship between vertebral body deformity and adjacent disc changes was assessed using correlation analysis, and the changes in the adjacent cranial and caudal discs was compared.

RESULTSThe Genant classification of the involved vertebral bodies was moderately correlated with Oner morphological scores (r=0.48, P<0.01), but not with the Pfirrmann signal scores of the adjacent cephalic discs or with the Genant or Pfirrmann scores of the adjacent caudal discs (P>0.05). The Oner classification of the adjacent cephalic discs was higher than that of the adjacent caudal discs (P<0.01), but their Pfirrmann classification did not differ significantly.

CONCLUSIONThe deformity of vertebral body affects the adjacent cephalic discs proportionally but not the adjacent caudal discs.

Fractures, Compression ; Humans ; Intervertebral Disc ; pathology ; Intervertebral Disc Degeneration ; Magnetic Resonance Imaging ; Spine ; pathology

BACKGROUNDAdjacent segment disease (ASD) is common after cervical fusion. The aim of this study was to evaluate the risk factors for ASD on X-ray and magnetic resonance imaging (MRI).

METHODSPatients included in this study had received revision surgeries after developing symptomatic ASD following anterior decompression and fusion. A control group that had not developed ASD was matched 1:1 by follow-up time and fusion segments. Plate-to-disc distances (PDDs), developmental cervical canal stenosis on X-ray, cervical disc degeneration grading, and cervical disc bulge impingements on preoperative MRI were measured and compared between the ASD group and the control group.

RESULTSThirty-four patients with complete radiographic data were included in the ASD group. The causative segments of ASD included nine cases of C3-4, 18 cases of C4-5, three cases of C5-6, and four cases of C6-7. The ASD occurred at the upper adjacent segments in 26 patients and at the lower adjacent segments in eight patients. PDD distributions were similar between the ASD group and the control group. Developmental cervical canal stenosis was a risk factor for ASD, with an odd ratio value of 2.88. Preoperative cervical disc degenerations on MRI were similar between the ASD group and the control group. In the upper-level ASD group, the disc bulge impingement was (19.7±9.7)%, which was significantly higher than that of the control group of (11.8±4.8)%.

CONCLUSIONSASD was more likely to develop above the index level of fusion. Developmental cervical canal stenosis and greater disc bulge impingement may be risk factors for the development of ASD.

Cervical Vertebrae ; pathology ; surgery ; Decompression, Surgical ; adverse effects ; Humans ; Intervertebral Disc Degeneration ; diagnosis ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Risk Factors ; Spinal Fusion ; adverse effects ; Spinal Stenosis ; diagnostic imaging

STUDY DESIGN: A prospective radiographic study of cervical spine with congenital monosegment fusion. PURPOSE: To evaluate the effect of cervical synostosis on adjacent segments and the vertebral morphology. OVERVIEW OF LITERATURE: There are numerous clinical studies of adjacent segment disease (ASD) after monosegment surgical fusion. However, there was no report on ASD in the cervical spine with congenital monosegment synostosis. METHODS: Radiograms of 52 patients, aged 5 to 90 years, with congenital monosegment synostosis (CMS) between C2 and C6, who complained of neck/shoulder discomfort or pain were studied. 51 were normally aligned and one was kyphotically aligned. RESULTS: Spondylosis was not found in the patients below 35 years of age. Only 12 out of 24 patients with normally aligned C2-3 synostosis had spondylosis in 19 more caudal segments, and only one at C3-4. A patient with kyphotic C2-3 had spondylolysis at C3-4. In 8 patients with C3-4 synostosis, spondylosis was found in only 9 caudal segments (4 at C4-5, 4 at C5-6, and 1 at C6-7). The caudate C4-5 disc was the most liable to degenerate in comparison with other caudate segments. Caudal corporal flaring and inwaisting of the synostotic vertebra were the features that were the most evident. In 2 of 9 C4-5 and 7 out of 10 C5-6 synostosis patients, spondylosis was found at the two adjacent cephalad and caudate segments, respectively. Only corporal inwaisting without flaring was found. In all cases, spondylosis was confined to the adjacent segments. More advanced spondylosis was found in the immediate caudal segment than the cephalad one. CONCLUSIONS: It is concluded that spondylosis at the mobile segments in a synostotic spine is thought to be a fusion-related pathology rather than solely age-related disc degeneration. Those data suggested that CMS definitely precipitated the disc degeneration in the adjacent segments.
Humans ; Intervertebral Disc Degeneration ; Pathology ; Prospective Studies ; Spine* ; Spondylolysis ; Spondylosis ; Synostosis*