Prospective Investigation of the Posterior Longitudinal Ligament and Disc Complex after Posterior Stabilization and Decompression Surgery in Patients With Non-OPLL (Ossification of the Posterior Longitudinal Ligament) Cervical Spondylotic Myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a prevalent cause of spinal cord dysfunction in adults, primarily from degenerative changes. The efficacy of treatment strategies, especially surgical approaches, remains debated. OBJECTIVE: This study aimed to assess the long-term impact of posterior fusion laminectomy on the posterior longitudinal ligament (PLL) thickness, disc complex, and myelomalacia signal changes in CSM patients. METHODS: A single-centre, prospective study from January 2020 to December 2021 included CSM patients without ossified posterior longitudinal ligament (OPLL). Magnetic resonance imaging (MRI) data from baseline, 6, and 12 months postoperatively were collected. Measurements on the MRI were performed using the Osirix MD software, focusing on the PLL width, myelopathic foci dimensions, and canal diameter. RESULTS: Out of the 82 initially enrolled patients, 64 were considered for analysis. Postoperatively, a significant reduction in PLL width and myelopathic foci dimensions was observed, alongside a considerable increase in the canal diameter. Clinical outcomes based on the Modified Japanese Orthopaedic Association (mJOA) scale also showcased marked improvements post-surgery. CONCLUSIONS: Posterior fusion laminectomy effectively reduces anterior pressure in CSM patients. This treatment may represent an optimal surgical approach for selected CSM cases. Furthermore, more extensive studies with extended follow-up are advocated.

A Convolutional Neural Network for Automated Detection of Cervical Ossification of the Posterior Longitudinal Ligament using Magnetic Resonance Imaging.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aimed to develop and validate a convolutional neural network (CNN) model to distinguish between cervical ossification of posterior longitudinal ligament (OPLL) and multilevel degenerative spinal stenosis using Magnetic Resonance Imaging (MRI) and to compare the diagnostic ability with spine surgeons. SUMMARY OF BACKGROUND DATA: Some artificial intelligence models have been applied in spinal image analysis and many of promising results were obtained; however, there was still no study attempted to develop a deep learning model in detecting cervical OPLL using MRI images. MATERIALS AND METHODS: In this retrospective study, 272 cervical OPLL and 412 degenerative patients underwent surgical treatment were enrolled and divided into the training (513 cases) and test dataset (171 cases). CNN models applying ResNet architecture with 34, 50, and 101 layers of residual blocks were constructed and trained with the sagittal MRI images from the training dataset. To evaluate the performance of CNN, the receiver operating characteristic curves of 3 ResNet models were plotted and the area under the curve were calculated on the test dataset. The accuracy, sensitivity, and specificity of the diagnosis by the CNN were calculated and compared with 3 senior spine surgeons. RESULTS: The diagnostic accuracies of our ResNet34, ResNet50, and ResNet101 models were 92.98%, 95.32%, and 97.66%, respectively; the area under the curve of receiver operating characteristic curves of these models were 0.914, 0.942, and 0.971, respectively. The accuracies and specificities of ResNet50 and ResNet101 models were significantly higher than all spine surgeons; for the sensitivity, ResNet101 model achieved better values than that of the 2 surgeons. CONCLUSION: The performance of our ResNet model in differentiating cervical OPLL from degenerative spinal stenosis using MRI is promising, better results were achieved with more layers of residual blocks applied.

Prevalence and Characteristics of Cervical Ossified Posterior Longitudinal Ligament in the Jewish Population.

BACKGROUND: Numerous studies have demonstrated an association between ethnic identity and the prevalence rate of cervical ossified posterior longitudinal ligament (C-OPLL). To date, its prevalence rate in the Jewish population has not been determined. The aim of this historical prospective study is to evaluate the prevalence and characteristics of C-OPLL in the Jewish population. METHODS: We performed a retrospective evaluation of imaging studies of all adult patients who underwent both cervical computed tomography and magnetic resonance imaging for all clinical indications within a span of 36 months between January 2017 and July 2020 at a single tertiary referral hospital located in central Israel. Identified C-OPLL carriers were interviewed by telephone. All the patients provided informed consent and then were questioned for current symptoms and demographics, including religion, Jewish ethnic identity, birthplace, parental birthplace and ethnic identity, and family history of spinal disorders. RESULTS: Overall, 440 participants were radiographically evaluated. The prevalence of C-OPLL in the Jewish population was 7.5% (33 of 440). The mean age of the C-OPLL carriers was 65.8 years. All the C-OPLL carriers were symptomatic at analysis. The carriers had an increased proportion with a Sephardic Jewish ethnic identity (65.4%), with a significantly high rate of homogeneous parental Jewish identity (92.4%), suggesting a prominent genetic contribution to the development of this condition. CONCLUSIONS: The prevalence of C-OPLL in the Jewish population in central Israel was 7.5%. This rate is significantly higher than that in other previously studied populations. To the best of our knowledge, this is the first study to identify the Jewish population as experiencing an increased prevalence of C-OPLL.

Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.

BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.

Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient.

Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.

Increased Cellular Expression of Interleukin-6 in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL. SUMMARY OF BACKGROUND DATA: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear. METHODS: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors. RESULTS: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1 . In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front. CONCLUSIONS: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL.

Which Morphological Features of Facet Diastasis Predict Thoracolumbar Posterior Ligamentous Complex Injury as Defined by Magnetic Resonance Imaging?

BACKGROUND: The association of various morphological features of facet diastasis with posterior ligamentous complex (PLC) injury has not been previously described. This study aims to determine the diagnostic value of facet diastasis subtypes for diagnosing thoracolumbar PLC injury. METHODS: We retrospectively reviewed 337 consecutive patients with acute thoracolumbar fractures who had computed tomography (CT) and magnetic resonance imaging (MRI) within 10 days of injury. Three and 5 reviewers evaluated MRI and CT images, respectively. Facet diastasis was subclassified as follows: Dislocated, no articular surface apposition; subluxed, incomplete articular surface apposition; and facet fracture articular process fractures which may be displaced ≥2 mm or otherwise undisplaced, facet joint widening (FJW) ≥ 3 mm. We examined the diagnostic accuracy and the multivariate associations of facet diastasis subtypes with PLC injury in MRI. RESULTS: Facet dislocation, subluxation, and displaced facet fracture yielded a high positive predictive value (PPV) for PLC injury (96%, 88%, and 94%, respectively). In contrast, undisplaced facet fracture and FJW yielded a moderate PPV for PLC injury (78%, and 45%, respectively). Facet dislocation, subluxation, and displaced facet fracture showed independent associations with PLC injury (adjusted odds ratio [AOR] = 38.4, 17.1, 13.4, respectively; P < 0.05). Undisplaced facet fracture and FJW were not associated with PLC injury (AOR = 3.9 [95% confidence interval, 0.49-38.4], P = 0.20) and (AOR = 1.94 [95% confidence interval, 0.48-7.13]; P = 0.20; P = 0.33), respectively. CONCLUSIONS: Facet dislocation, subluxation, and displaced facet fracture, but not undisplaced facet fracture or FJW, were independently associated with PLC injury. Therefore, we propose to define facet diastasis as a surrogate marker of PLC injury in MRI based on these morphologies.

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. RESULTS: Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. CONCLUSIONS: We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.

BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI). CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed. CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.

Clinical Indicators of Surgical Outcomes After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes. MATERIALS AND METHODS: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses. RESULTS: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery. CONCLUSIONS: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL.

Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1.

Ossification of the posterior longitudinal ligament (OPLL) is an emerging spinal disease caused by heterotopic ossification of the posterior longitudinal ligament. The pathological mechanism is poorly understood, which hinders the development of nonsurgical treatments. Here, we set out to explore the function and mechanism of small extracellular vesicles (sEVs) in OPLL. Global miRNA sequencings are performed on sEVs derived from ligament cells of normal and OPLL patients, and we have showed that miR-320e is abundantly expressed in OPLL-derived sEVs compare to other sEVs. Treatment with either sEVs or miR-320e significantly promote the osteoblastic differentiation of normal longitudinal ligament cells and mesenchymal stem cells and inhibit the osteoclastic differentiation of monocytes. Through a mechanistic study, we find that TAK1 is a downstream target of miR-320e, and we further validate these findings in vivo using OPLL model mice. Together, our data demonstrate that OPLL ligament cells secrete ossification-promoting sEVs that contribute to the development of ossification through the miR-320e/TAK1 axis.

Full-Endoscopic Resection of a Recurrent Posterior Longitudinal Ligament Cyst: Technical Note.

BACKGROUND: Posterior longitudinal ligament cysts are very rare lesions and do not usually recur. Microscopic resection is commonly performed. The aim of this article was to report a case of recurrent posterior longitudinal ligament cyst that benefited from full-endoscopic resection. METHODS: We used the 25° endoscope of the RIWOspine set for interlaminar approach. A step-by-step description of the surgical technique was presented. RESULTS: Clinical evolution was favorable. The patient remained pain-free 1 month after surgery, and postoperative magnetic resonance imaging showed complete resection of the cyst. CONCLUSIONS: Endoscopy is a safe and feasible approach for posterior longitudinal ligament cysts, including unusual recurrent cases.

Bilateral facet effusion is a risk factor for segmental instability with cervical injury without vertebral fracture.

Magnetic resonance imaging (MRI) is effective in identifying cervical spine injury after trauma. However, cervical instability without major bone injury or dislocation is challenging to assess. Hence, the current study aimed to investigate and compare the MRI and radiography findings of segmental instability in patients with cervical spine injury. We investigated 34 participants with cervical spine injury without vertebral fracture. Based on the radiography findings, the participants were categorized into two: group A with segmental instability (n = 11) and group B without segmental instability (n = 23). Both groups were compared in terms of the presence of segmental instability on radiography and MRI. Anterior longitudinal ligament (ALL) injury, disc injury, and bilateral facet effusion were observed in 6/11, 5/11, and 7/11 patients in group A and in 5/23, 2/23 and 7/23 patients in group B, respectively. The results showed significant differences (p < 0.05). Moreover, 2 and 10 of 11 patients in group A and 16 and 7 of 23 patients in group B presented with hemi lateral facet effusion and paravertebral muscle injury, respectively. However, the results did not significantly differ. According to a logistic regression analysis, bilateral facet effusion after trauma was associated with cervical segmental instability (odd ratio: 10.6, 95% confidence interval: 1.31-84.7). Facet joint effusion might be caused by capsule injury during trauma. Most participants with segmental instability had ALL, disc, and flavum injury and bilateral facet effusion. Therefore, we need to consider bilateral facet effusion with other soft tissue damage of the cervical spine as an association factor to show the instability.

Machine Learning Approach in Predicting Clinically Significant Improvements After Surgery in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A retrospective analysis of prospectively collected data. OBJECTIVE: This study aimed to create a prognostic model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using machine learning (ML). SUMMARY OF BACKGROUND DATA: Determining surgical outcomes helps surgeons provide prognostic information to patients and manage their expectations. ML is a mathematical model that finds patterns from a large sample of data and makes predictions outperforming traditional statistical methods. METHODS: Of 478 patients, 397 and 370 patients had complete follow-up information at 1 and 2 years, respectively, and were included in the analysis. A minimal clinically important difference (MCID) was defined as an acquired Japanese Orthopedic Association (JOA) score of ≥2.5 points, after which a ML model that predicts whether MCID can be achieved 1 and 2 years after surgery was created. Patient background, clinical symptoms, and imaging findings were used as variables for analysis. The ML model was created using LightGBM, XGBoost, random forest, and logistic regression, after which the accuracy and area under the receiver-operating characteristic curve (AUC) were calculated. RESULTS: The mean JOA score was 10.3 preoperatively, 13.4 at 1 year after surgery, and 13.5 at 2 years after surgery. XGBoost showed the highest AUC (0.72) and high accuracy (67.8) for predicting MCID at 1 year, whereas random forest had the highest AUC (0.75) and accuracy (69.6) for predicting MCID at 2 years. Among the included features, total preoperative JOA score, duration of symptoms, body weight, sensory function of the lower extremity sub-score of the JOA, and age were identified as having the most significance in most of ML models. CONCLUSION: Constructing a prognostic ML model for surgical outcomes in patients with OPLL is feasible, suggesting the potential application of ML for predictive models of spinal surgery.Level of Evidence: 4.

Effect of teriparatide on ligamentum flavum mesenchymal stem cells isolated from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) within the spinal canal sometimes leads to severe myelopathy. Teriparatide (TPD) is a recombinant human parathyroid hormone (PTH) (1-34), which promotes osteogenesis of mesenchymal stem cells (MSCs) via PTH 1 receptor (PTH1R). Although ligamentum flavum (LF)-MSCs from patients with OPLL have a high osteogenic potency, the effect of TPD on them remains unknown. In this study, we determined PTH1R expression in LF-MSCs from patients with OPLL and investigated whether TPD promotes osteogenic differentiation in them. First, LF-MSCs were isolated from patients with OPLL and cervical spondylotic myelopathy (CSM) (controls). Cultured LF-MSCs were treated with different concentrations of TPD on days 0, 7, and 14. On day 21, osteogenic gene expression was quantified. Mineralization was measured based on optical density after Alizarin Red S staining. LF-MSCs from both groups expressed PTH1R at the same level. TPD did not enhance osteogenic gene expression and mineralization in LF-MSCs from both groups. TPD did not promote the osteogenic differentiation of LF-MSCs from patients with OPLL. Thus, it may be safe for patients with OPLL. However, further confirmation of our results with in vivo studies is necessary.

Promoting effect of long non-coding RNA SNHG1 on osteogenic differentiation of fibroblastic cells from the posterior longitudinal ligament by the microRNA-320b/IFNGR1 network.

Long non-coding RNAs (lncRNAs) have been noted to influence the progression of ossification of posterior longitudinal ligament (OPLL). The work aims to probe the effect of lncRNA SNHG1 on osteogenic differentiation of ligament fibroblastic cells (LFCs). Aberrantly expressed lncRNAs in ossified PLL tissues were screened out by microarray analysis. Gain- and loss-of function experiments of SNHG1 were performed to identify its role in osteogenic differentiation of LFCs. The downstream molecules of SNHG1 were explored. Altered expression of miR-320b was introduced in LFCs as well. The interactions among SNHG1, miR-320b and IFNGR1 were identified. Consequently, SNHG1 was found highly expressed in OPLL patients. Silencing of SNHG1 inhibited BMP-2, RUNX2 and OCN expression and the ALP activity and reduced osteogenic differentiation of LFCs. Importantly, SNHG1 could and upregulate IFNGR1 through serving as a sponge for miR-320b. Over-expression of miR-320b inhibited osteogenic differentiation of LFCs and inactivated the JAK/STAT signaling pathway. Further administration of Fedratinib, a JAK2-specific agonist, increased osteogenic differentiation of LFCs. To conclude, the study suggested that SNHG1 could upregulate IFNGR1 by sequestering miR-320b and activate the JAK/STAT signaling. Silencing of SNHG1 could reduce the osteogenic differentiation and mineralization of LFCs. The study may offer new insights into OPLL treatment.

Effects of oophorectomy on the lumbar spine of Wistar rats submitted to vibratory platform treatment / Efectos de la ooforectomía en la columna lumbar de las ratas de Wistar sometidas a tratamiento con plataforma vibratoria

INTRODUCTION: This study evaluated the effect of the vibratory platform on the lumbar spine morphology of Wistar rats sub-mitted to hormonal deprivation by oophorectomy. MATERIAL AND METHOD: Twenty rats were divided into four groups: Pseudo-oophorectomy (GP), Pseudo-oophorectomy Treated (GPT ), Oophorectomy (GO), Oophorectomy Treated (GOT ). After 60 days of postoperative, the treated groups started exercises on a vibratory platform in the frequency parameters of 60 Hz, alternating vibration with amplitude of 2 mm, acceleration of 57.6 m/s² and time of 10 minutes, three times in the during the four week period. Following the euthanasia of the animals, the lumbar spine was dissected and processed for analysis of the anterior and posterior longitudinal ligaments, intervertebral disc height (IVD), nucleus pulposus (NP) height, radiographic density of the lumbar vertebrae and IVD morphology. RESULTS: The results showed a decrease in the height of the NP associated to the GO and morphological alterations such as lamellar disorganization and presence of rifts in the fibrous ring, alterations of the structural limits and decrease of the NP cavity; while the other groups presented organized lamellae, peripheral and nuclear region well delimited and wide cavity of the nucleus. CONCLUSION: In this way, it can be concluded that the oophorectomy protocol promoted a decrease in the height of the NP of the IVD and that the exercise in the vibratory platform did not generate lesions in the analyzed tissues, as well as preserved the structural organization of the IVD and the height of the NP of oophorectomized rats

INTRODUCCIÓN: Este estudio evaluó el efecto de la plataforma vibratoria sobre la morfología de la columna lumbar de las ratas de Wistar sometidas a privación hormonal por ooforectomía. MATERIAL Y MÉTODO: Veinte ratas fueron divididas en cuatro grupos: Pseudo-ooforectomía (GP), Pseudo-ooforectomía tratada (GPT ), Ooforectomía (GO), Ooforectomía tratada (GOT ). Después de 60 días de postoperatorio, los grupos tratados iniciaron los ejercicios en una plataforma vibratoria en los parámetros de frecuencia de 60 Hz, alternando vibración con amplitud de 2 mm, aceleración de 57,6 m/s² y tiempo de 10 minutos, tres veces en el período de cuatro semanas. Tras la eutanasia de los animales, la columna lumbar fue diseccionada y procesada para el análisis de los ligamentos longitudinales anteriores y posteriores, la altura del disco intervertebral (DIV ), la altura del núcleo pulposo (NP), la densidad radiográfica de las vértebras lumbares y la morfología del DIV. RESULTADOS: Los resultados mostraron una disminución en la altura del PN asociado al GO y alteraciones morfológicas tales como desorganización laminar y presencia de fisuras en el anillo fibroso, alteraciones de los límites estructurales y disminución de la cavidad del PN; mientras que los otros grupos presentaron láminas organizadas, región periférica y nuclear bien delimitadas y amplia cavidad del núcleo. CONCLUSIÓN: De esta manera, se puede concluir que el protocolo de ooforectomía promovió una disminución en la altura del PN de la IVD y que el ejercicio en la plataforma vibratoria no generó lesiones en los tejidos analizados, además de preservar la organización estructural de la IVD y la altura de la NP de las ratas ooforectomizadas

Expression Analysis of Susceptibility Genes for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine in Human OPLL-related Tissues and a Spinal Hyperostotic Mouse (ttw/ttw).

STUDY DESIGN: Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. OBJECTIVE: The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study. SUMMARY OF BACKGROUND DATA: Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL. METHODS: Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain. RESULTS: Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples. CONCLUSION: Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL. LEVEL OF EVIDENCE: N/A.

Abusive Pediatric Thoracolumbar Fracture Due to Forced Hyperextension: Case Report, Biomechanical Considerations, and Review of the Literature.

Pediatric thoracolumbar fractures are rare due to the physiological differences which afford greater resilience to the immature spine. Most pediatric thoracolumbar fractures occur as the result of high energy trauma, such as motor vehicle accidents, and modes of reasonable accidental injuries are limited by age and developmental capabilities of the child. These fractures can occur as the result of inflicted blunt force trauma and child abuse, and in most cases, the mechanism of injury to the spine is not known. We report the death of a 29-month-old man due to blunt force trauma to the back and forced hyperextension of the thoracolumbar spine causing fracture of the fourth lumbar (L4) vertebral body. A complete forensic examination revealed a previous healing fracture of the anterior aspect of the L4 vertebral body, with acute disruption of the anterior longitudinal ligament overlying the fracture site, complete fracture of the vertebral body, and fatal retroperitoneal hemorrhage. We present a review of the biomechanical considerations of the pediatric spine, a survey of pediatric spinal fractures, and a review of the literature on pediatric abusive thoracolumbar fractures. In this case, there was never a provided explanation for how the injury occurred; however, understanding the biomechanics of the pediatric spine allowed for the determination of the mechanism, force required to produce this specific pattern of abusive spinal injury, and the manner of death.