Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy): possible pathomechanism of human cervical compressive myelopathy

Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2-C3 and exhibited progressive paralysis

Effects of malalignment and disease activity on osteophyte formation in knees of rheumatoid arthritis patients.

PURPOSE:Rheumatoid arthritis (RA) patients with secondary osteoarthritis (OA) in a knee joint following a total knee arthroplasty (TKA) procedure have been increasing. Here, we investigated osteophyte formation in knee joints of RA patients and associated factors.METHODS:We retrospectively examined findings of 35 knees in 30 RA patients (26 females, 4 males; mean age: 63.0 years; median disease duration: 15 years) who underwent TKA, including preoperative anteroposterior view radiographs of the knee joint. Using the ImageJ software package, osteophyte size in the medial femur (MF), medial tibia (MT), lateral femur (LF), and lateral tibia (LT) regions was also determined.RESULTS:The mean femorotibial angle was 179°, while Larsen grade was 2 in 1, 3 in 12, 4 in 18, and 5 in 2 patients. Osteophyte sizes in the MF, MT, LF, and LT regions were 37.2, 17.0, 27.2, and 4.57 mm2, respectively, and significantly greater in the medial compartment (MC; MF+MT) than the lateral compartment (LC; LF+LT) (p < 0.001). In varus cases, osteophyte size in the MC was significantly larger than normal and valgus cases (p = 0.0016). Furthermore, osteophyte size in the MC was negatively correlated with the inflammatory markers C-reactive protein (r = -0.492, p = 0.0027) and erythrocyte sedimentation rate (r = -0.529, p = 0.0016), whereas that in the LC was negatively correlated with disease activity (r = -0.589, p = 0.0023).CONCLUSION:Our results suggest that alignment and disease activity influence osteophyte formation in RA patients, with secondary OA a more prominent symptom in RA patients with controlled inflammation

Incidence of Cranial Adjacent Segment Disease after Posterior Lumbar Interbody Fusion Using the Cortical Bone Trajectory Technique for the Treatment of Single-Level Degenerative Lumbar Spondylolisthesis; More than a 2-Year Follow-Up.

Introduction:Posterior lumbar interbody fusion (PLIF) is a widely used effective, safe, and established treatment for degenerative spinal disorders. Adjacent segment disease (ASD) is one of the serious concerns governing the clinical results following spinal fusion surgery. Cortical bone trajectory (CBT) is an alternative and less-invasive technique for lumbar pedicle screw placement. Its unique medial and caudal entry point has the potential to prevent an iatrogenic facet joint violence leading to the ASD; however, the incidence of ASD following PLIF using the CBT technique (CBT-PLIF) remains unknown.Methods:Among patients surgically treated with CBT-PLIF in our institute, 52 consecutive patients (13 males, 39 females) with single-level degenerative lumbar spondylolisthesis (DLS) who were followed up for at least 24 months were exclusively enrolled. Their clinical and radiological features, including the incidence of radiographical and symptomatic ASD and significantly associated factor for the developing radiographical ASD, were retrospectively measured.Results:In the present study, we could confirm significant neurological improvement and reduction of the spondylolisthesis with mean follow-up period of 43 months. Radiographical and symptomatic ASD was observed in 14 (27%) and 2 (3.8%) cases, respectively. We compared these two groups and found that the latest lumbar lordosis was significantly different between the two groups, but not in age, body mass index, and Japan Orthopaedic Association score. Two patients with symptomatic ASD required additional surgical treatment around 1 year following the initial surgery.Conclusions:The present study, even though it is preliminary, revealed that CBT-PLIF can achieve a neurological improvement and an effective reduction of spondylolisthesis for the treatment of single-level DLS. The CBT technique is capable of reducing the incidence of ASD compared with the traditional technique; however, we must keep in mind that appropriate postoperative lumbar lordosis should be achieved. Larger, longer-term follow-up studies are required to elucidate the clinical output of CBT-PLIF

Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro

<p>Abstract</p> <p>Background</p> <p>The application of mechanical insults to the spinal cord results in profound cellular and molecular changes, including the induction of neuronal cell death and altered gene expression profiles. Previous studies have described alterations in gene expression following spinal cord injury, but the specificity of this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile stresses on cultured spinal cord cells from E15 Sprague-Dawley rats, using the FX3000^®Flexercell Strain Unit. We examined cell morphology and viability over a 72 hour time course. Microarray analysis of gene expression was performed using the Affymetrix GeneChip System^®, where categorization of identified genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. Changes in expression of 12 genes were validated with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to "apoptosis" and 17 genes related to "response to stimulus". KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis.</p> <p>Conclusions</p> <p>We have demonstrated that spinal cord cells undergo cell death in response to cyclic tensile stresses, which were dose- and time-dependent. In addition, we have identified the up regulation of various genes, in particular of the MAPK pathway, which may be involved in this cellular response. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.</p