Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.

BACKGROUND AND OBJECTIVES: Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. METHODS: A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. RESULTS: The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. CONCLUSION: The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.

Factors affecting titanium mesh cage subsidence in single-level anterior cervical corpectomy and fusion for ossification of the posterior longitudinal ligament.

PURPOSE: To analyze risk factors of titanium mesh cage (TMC) subsidence in single-level anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: TMC subsidence is defined as the reduction of the adjacent vertebral bodies by ≥ 2 mm. Patients with cervical OPLL who were treated with single-level ACCF between January 2019 and May 2021 were retrospectively analyzed in two groups: patients with TMC subsidence as Group S and patients with no TMC subsidence as Group N during the one-year follow-up period. The degree of distraction of surgical segment and correction of the cervical curvature was measured to analyze their relationship with TMC subsidence. RESULTS: A total of 128 patients were included in Group S, and 138 patients were included in Group N. There was no significant difference in patient demographics and complications between the two groups. The degree of distraction in Group S was significantly higher than that in Group N (11.4% ± 7.6% vs. 4.7% ± 9.7%, P < 0.01). The change of C2 to C7 Cobb angle (α) in Group S was significantly greater than that in Group N (5.7 ± 2.7 vs. 1.4 ± 4.7, P < 0.01), and the change of interspinous process distance (SPD) in Group S was also significantly greater than that in Group N (7.0 ± 4.2 vs. 4.1 ± 2.7, P < 0.01). The JOA score and JOA recovery rate were not statistically different between the two groups. CONCLUSIONS: Intraoperative selection of overlength TMC in single-level ACCF for OPLL, over-distraction and excessive correction of the cervical curvature may cause TMC subsidence after surgery. No significant impact of TMC subsidence on the surgical outcome was observed during the 1-year follow-up period.

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.

Diagnostic accuracy of cervical spine imaging to predict thoracic ossification of the posterior longitudinal ligament: Retrospective chart review.

PURPOSE: To analyze the significance of ossification index of cervical posterior longitudinal ligament as a risk factor for thoracic OPLL (ossification of the posterior longitudinal ligament) in patients with cervical OPLL. METHODS: We retrospectively analyzed the clinical data of cervical OPLL patients in Changzheng hospital, who received chest CT scans for screening of COVID-19, and included 87 patients into this study. According to the radiographic evidence, 87 patients were divided into CT group(cervical OPLL combined with thoracic OPLL）and C group(cervical OPLL group). We measured the cervical OS index (ossification index), and analyzed the relationship between thoracic OPLL and cervical OS index. RESULTS: There was no difference of age、sex、duration of symptoms、comorbidity between the 2 groups(P＞0.05). The mean cervical OS index was higher in the CT group than in the C group (8 ± 2 VS 3 ± 2，P＜0.001). CONCLUSIONS: Patients with cervical OS index ＞8 was considered as "high risk" of tandem OPLL, while with value ≤ 4 was considered as "low risk". Index between 5 and 8 were considered as "middle risk". This study demonstrated that the cervical OS index may be used as an indicator of thoracic OPLL in patients with cervical OPLL, with a high diagnostic accuracy.

Aponeurosis discission, a low-detergent method for tissue-engineered acellular ligament scaffolds.

Detergent treatment is the most commonly used method for the decellularization of ligaments and tendon grafts. However, it is well recognized that detergent treatment can also adversely affect the extracellular matrix. This study found that discission into the aponeurosis layer of the patellar tendon (PT) before decellularization is conducive to extracting cells from the PT using a low quantity of detergent in a short time period. The acellular aponeurosis discission ligament (AADL) retains its native collagen fibril structure and mechanical properties. Moreover, the PT retained cell and tissue compatibility in vitro and in vivo. After implantation into a defective allogeneic PT, we found that the AADL healed well in the host, and its collagen structure exhibited gradual improvement 12 months after implantation with satisfactory reconstruction. IMPACT: The aponeurosis of tendons/ligaments is the main barrier to achieving complete decellularization, and it thus prevents complete recellularization for applications in tissue engineering. Aponeurosis can obstruct the removal of cell components. We found that excising the aponeurosis before decellularization allows for the removal of cellular components with a reduced amount of detergent, thus improving the biological properties of the acellular ligament. To the best of our knowledge, no similar studies have been performed. Graphical abstract.

Mid-term follow-up outcomes of single-level cervical total disc replacement versus anterior cervical discectomy and fusion for the treatment of cervical disc degenerative disease.

BACKGROUND: To evaluate the clinical and radiographic results of cervical total disc replacement (CTDR) and anterior cervical discectomy and fusion (ACDF) in the treatment of single-level cervical disc degenerative disease with a mid-term follow-up period. METHODS: Seventy-two patients with C5/6 single-level cervical degenerative disc disease refractory to conservative interventions were randomly assigned to two groups: ACDF and CTDR. Clinical outcomes were assessed by using the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). Radiographic evaluations included range of motion (ROM), Cobb angles, heterotopic ossification (HO) and adjacent segment degeneration during follow-up. RESULTS: Sixty-nine patients (35 CTDR and 34 ACDF) were followed up over 4 years (mean 50.3 months). At 1 month postoperation, the NDI scores in CTDR patients were significantly higher than those in ACDF patients, especially in the work, driving and recreation aspects. There was significant improvement in global ROM in CTDR patients than in ACDF patients. The postoperative ROM of the C4/5 segment in ACDF patients increased significantly, and no significant difference was shown in other adjacent segments. The occurrence of HO was 42.9% (15/35) in the CTDR group at the last followup, with Grade I in 3 cases, Grade II in 11 cases and Grade III in 1 case. CONCLUSIONS: CTDR is an effective method in the treatment of single-level cervical disc degenerative disease. Compared to ACDF, CTDR is superior in the early improvement of quality of life, and restoration of segmental motion despite radiographic evidence of HO during a mid-term follow-up period.

Risk Factors for Poor Prognosis of Spinal Cord Injury without Radiographic Abnormality Associated with Cervical Ossification of the Posterior Longitudinal Ligament.

PURPOSE: To investigate the factors associated with the prognosis of spinal cord injury without radiographic abnormality (SCIWORA) accompanied by cervical ossification of the posterior longitudinal ligament (C-OPLL). METHODS: We retrospectively investigated 287 patients with SCIWORA associated with C-OPLL, who were admitted within 30 days after trauma to our facility between August 2014 and August 2018. All patients were divided into the good or poor prognosis group. Patient demographics were analyzed. Besides, occupying ratio on CT and spinal cord high signal changes in MRI T2WI were measured and recorded. Multivariate linear regression was applied to analyze the correlation of prognosis with spinal cord high signal changes in MRI T2WI, cause of injury, and occupying ratio. RESULTS: Occupying ratio of ossification mass was 43.5 ± 10.7% in the poor prognosis group and 27.3 ± 7.7% in the good prognosis group. The occurrence rate of high signal changes in MRI T2WI was 84.2% in the poor prognosis group and 41.3% in the good prognosis group. Poor prognosis was correlated with high occupying ratio and spinal cord high signal changes in MRI T2WI. In the patient with SCIWORA associated with C-OPLL, ROC curve of occupying ratio showed 30% as a predictor for the poor prognosis. Among the 92 patients with occupying ratio ≤ 30%, poor prognosis was observed in 5 cases (5.4%), whereas in the 72 cases with occupying ratio > 30%, poor prognosis was seen in 33 cases (45.8%). Postoperative AIS grade at final follow-up in occupying ratio > 30% group was significantly worse. CONCLUSIONS: Patients suffering from SCIWORA with C-OPLL have poor prognosis when they have higher occupying ratio of ossification mass and spinal cord high signal changes in MRI T2WI. The cut-off value of occupying ratio for predicting the poor prognosis was 30% in patients with SCIWORA associated with C-OPLL.

Clinical and Radiographic Outcomes of Combined Posterior Transfacet Screw Fixation and Anterior Cervical Discectomy and Fusion Surgery for Unilateral Cervical Facet Fracture with Traumatic Disc Herniation: A Retrospective Cohort Study.

INTRODUCTION: Combined lateral mass screw-rod (LMSR) fixation and anterior cervical discectomy and fusion (ACDF) surgery is currently the most widely described and accepted procedure for subaxial cervical facet fracture with traumatic disc herniation. Recent biomechanical studies have demonstrated that the use of transfacet screw (TFS) can be considered as a simple alternative method to LMSR. However, to date, little is known about the feasibility and effectiveness of TFS in the combined approach. The aim of this study was to compare the clinical and radiographic results of TFS + ACDF surgery and LMSR + ACDF surgery, and to provide a less invasive alternative technique for spine surgeons. METHOD: We retrospectively reviewed patients with unilateral cervical facet fracture with traumatic disc herniation who had undergone TFS + ACDF (N = 36) or LMSR + ACDF (N = 34) with a minimum 2-year follow-up. Clinical assessments, which included American Spinal Injury Association impairment scale (AIS), visual analog scale for neck pain (VASSNP) score and patient satisfaction, were made before surgery and at follow-up. For the radiographic outcomes, the instability parameters of segmental kyphosis and sagittal translation were measured. RESULTS: The demographic characteristics of the two groups of patients were similar. In terms of clinical outcomes, both two groups were associated with significant improvements at the final follow-up. There were no significant between-group differences in VASSNP score or patient satisfaction (both P > 0.05). The LMSR + ACDF group suffered more blood loss and had longer operative time (mean 206.0 ml; mean 274.4 min, respectively) than in the TFS + ACDF group (mean 110.0 ml; mean 142.8 min, respectively) (P < 0.001 for both comparisons). For the radiographic results, the segmental kyphosis and sagittal translation were significantly corrected after surgery in both groups (P < 0.001 for both groups), and no significant differences were found between groups at the last follow-up (P > 0.05). CONCLUSION: In the absence of any self-evident clinical and radiographic benefits of one technique over the other (TFS + ACDF vs. LMSR + ACDF), we recommend combined TFS + ACDF surgery as a safe and less invasive alternative treatment for unilateral cervical facet fractures with traumatic disc herniation, as it was associated with a shorter duration of surgery and lower estimated blood loss than LMSR + ACDF surgery.

Traumatic cervical spinal cord injury: relationship of MRI findings to initial neurological impairment.

PURPOSE: To quantify the degree of available space for the cord and cord swelling in patients following traumatic cervical spinal cord injury (TCSCI), and to assess the relationship among the available space for the cord, cord swelling, and the severity of neurological impairment. METHODS: This study included 91 patients. The following indexes were measured by two blinded observers: maximum cord available area (CAAmax) and maximum cord swelling area (CSAmax). The American Spinal Injury Association (ASIA) impairment scale (AIS) grades were used to evaluate the extent of neurological injury. Relationship among CAAmax, CSAmax, and initial AIS grades was assessed via univariate and multivariate analyses. RESULTS: Patients who were AIS grade A (complete injury) demonstrated significantly greater median CAAmax and CSAmax than AIS grade C or D (incomplete injury) (P < 0.01). Multivariate analysis identified only CAAmax (OR 20.88 [95% CI 1.50-291.21]; P = 0.024) and CSAmax (OR 17.84 [95% CI 1.15-276.56]; P = 0.039) were identified as independently influencing the likelihood of complete injury at the initial assessment. The classification accuracy was best for CAAmax and CSAmax; areas under the curve were 0.8998 (95% CI 0.7881-1.0000) and 0.9167 (95% CI 0.8293-1.0000), respectively. CONCLUSION: The present study provides a novel radiologic method for identifying the severity of TCSCI with T2-weighted MRI findings. Greater available space for the cord (CAAmax > 38%) and cord swelling (CSAmax > 29%) can be used to identify patients at risk for TCSCI and both imaging characteristics are associated with an increased likelihood of severe neurological deficits. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Three-dimensional reduction method with a modified C2 isthmus screw in irreducible atlantoaxial dislocation: a technical note.

BACKGROUND: Three-dimensional reduction plays a vital role in surgical reduction of irreversible atlantoaxial dislocation (IAAD). However, the most commonly used combination of C1 pedicle screw (PS) or lateral mass screw (LMS) and C2 PS or isthmus screw often fails to achieve satisfactory reduction at one time. The difficulty is usually caused by short anteroposterior and vertical distance between heads of C1 and C2 screws, which lack enough space for reduction operation. The objective of this study is to describe a three-dimensional reduction method with a modified C2 isthmus screw and to illustrate its advantage and effectiveness for IAAD. METHODS: Twelve patients with IAAD underwent reduction and fixation with modified C2 isthmus screw combined with C1 PS or LMS, fusion with autologous bone graft. The insertion point was lateral to the intersection of caudal edge of C2 lamina and lateral mass, with a trajectory towards C2 isthmus, via lateral mass. The three-dimensional reduction was achieved through pulling and distracting. Radiographic evaluation included anteroposterior and direct distance between different insertion points, the occipitoaxial angle (O-C2A), clivus-canal angle (CCA) and cervicomedullary angle (CMA). Clinical outcomes evaluation included the Japanese Orthopaedic Association (JOA) score, Visual analog scale (VAS) and Neck Disability Index (NDI). RESULTS: All the patients maintained effective reduction during the follow-up. The anteroposterior and direct distance was significantly higher in modified C2 isthmus screw than C2 PS whether combined with C1 PS or LMS (P < 0.05). The degree of O-C2A, CCA and CMA, JOA score, NDI, and VAS were significantly improved after the surgery (P < 0.05). CONCLUSIONS: Three-dimensional reduction method with a modified C2 isthmus screw is effective and safe in managing IAAD. It can increase the anteroposterior and vertical distance between the heads of C1 and C2 screws, which is benefit for the three-dimensional reduction operation of IAAD.

Treatment for tuberculosis of the subaxial cervical spine: a systematic review.

PURPOSE: To systematically review the clinical manifestations and treatment outcomes of patients with subaxial cervical spinal tuberculosis (SCS-TB) and evaluate the current evidence for surgical or nonsurgical treatment. METHOD: A systematic review was performed using the PubMed, ScienceDirect, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies published in English from January 2000 to December 2018 were included in the search. A reference lists search of relevant articles was also conducted for other potential references. The risk of bias was assessed with the 13-item criteria recommended by the Cochrane Back and Neck Group and the Methodological Index for Non-Randomized Studies. RESULTS: Fifteen articles were included with a total of 456 patients, of which only 1 study was randomized and fourteen were nonrandomized. The most common symptom reported was neck pain and stiffness, and the most common segment involved was C5. Of the 456 patients, 329 (72.1%) were treated surgically. Most experienced neurologic recovery after surgery. Instrumentation resulted in maintenance of the correction of alignment throughout the follow-up period. The use of radical debridement is still in debate. CONCLUSIONS: Anti-TB therapy is necessary for all SCS-TB patients, including those underwent surgical management. For patients with neurological dysfunction, the surgical method with decompression and instrumentation could provide better cervical spinal alignment and stability. For adult, the radical debridement remains in debate, while for children, radical debridement may cause the development of progressive kyphosis during growth. Larger randomized comparative studies with longer follow-up times are needed.

Consensus statement on diagnosis and treatment of cervical ossification of posterior longitudinal ligament from Asia Pacific Spine Society (APSS) 2020.

PURPOSE: The study aimed to develop an evidence-based expert consensus statement on diagnosis and treatment of cervical ossification posterior longitudinal ligament (OPLL). METHOD: Delphi method was used to perform such survey, and the panel members from Asia Pacific Spine Society (APSS) 2020 were invited to answer the open-ended questions in rounds 1 and 2. Then the results were summarized and developed into a Likert-style questionnaire for voting in round 3, and the level of agreement was defined as 80%. In the whole process, we conducted a systematic literature search on evidence for each statement. RESULTS: Cervical OPLL can cause various degrees of neurological symptoms, an it's thought to be more common in Asia population. CT reconstruction is an important imaging examination to assist diagnosis and guide surgical choice. Segmental, continuous, mixed, and focal type is the most widely used classification system. The non-surgical treatment is recommended for patients with no or mild clinical symptoms, or irreversible neurological damage, or failed surgical decompression, or condition cannot tolerant surgery, or refusing surgery. As OPLL may continue to develop gradually, surgical treatment would be considered in their course inevitably. The surgical choice should depend on various conditions, such as involved levels, thickness, and type of OPLL, skill-experiences of surgeons, which are listed and discussed in the article. CONCLUSION: In this statement, we describe the clinical features, classifications, and diagnostic criteria of cervical OPLL, and review various surgical methods (such as their indications, complications), and provide a guideline on their choice strategy.

How Does Cervical Sagittal Balance Change After Hangman Fracture Treated with Anterior or Posterior Approach Surgery?

OBJECTIVE: To assess and compare clinical outcomes and sagittal balance after unstable hangman fracture between C2-C3 anterior discectomy and fusion (ACDF) and posterior C2-C3 short-segment fixation and fusion. METHODS: A total of 45 patients underwent ACDF (20 patients) and posterior C2-C3 short-segment fixation and fusion (25 patients) between March 2005 and June 2013. Visual analog scale, Neck Disability Index, Odom grading system, American Spinal Injury Association Impairment Scale (AIS), C2-C3 angle, displacement of C2-C3 (DC2-C3), occiput-C2 angle (O-C2 angle), cervical lordosis (CL), and C2-C7 sagittal vertical axis (cSVA) were assessed preoperatively and at final follow-up. RESULTS: The follow-up duration was 20.0 months (range, 18.0-21.0 months) in the anterior group and 19.0 months (range, 18.0-20.0 months) in the posterior group. Satisfactory bony fusions were achieved in 2 groups. The VAS score and NDI score were significantly lower than their respective preoperative score in each group (P < 0.001), whereas there was no difference between 2 groups (P = 0.78; P = 0.85). A statistically significant decrease of O-C2 angle and cSVA between preoperative and postoperative data was found in each group (P < 0.001), and CL increased statistically (P < 0.001). For O-C2 angle, CL, and cSVA, the changes of parameters after the posterior approach were more significant than after the anterior approach (P < 0.05). CONCLUSIONS: Both anterior and posterior surgical techniques are effective for unstable hangman fracture and both can restore the sagittal balance of the cervical spine. Furthermore, the posterior approach has an advantage over the anterior approach in promoting recovery of cervical sagittal balance.

Choice of the Open Side in Unilateral Open-Door Laminoplasty for Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: Retrospective study. OBJECTIVE: To determine the optimal open side in unilateral open-door laminoplasty (UODL) for lateral cervical ossification of posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: No literature has reported which side of the vertebral arch should be chosen as the open side in UODL for lateral cervical OPLL. METHODS: Patients with lateral cervical OPLL who were treated with UODL between 2013 and 2018 were retrospectively analyzed in two groups: Group A, where the open side was contralateral to the ectopic bone, and Group B, where the open side was ipsilateral to the ectopic bone. The Japanese Orthopaedic Association (JOA) Score, JOA recovery rate, spinal canal enlargement rate, cervical range of motion (ROM), and spinal cord area (SCA) were measured to evaluate and compare the clinical outcomes between the two groups. Statistical analysis was performed by t test and Hotelling T2 test. RESULTS: There was no significant difference in patient demographics and major complications between the two groups. The postoperative JOA Score and JOA recovery rate in Group A were significantly higher than those in Group B. There was no significant difference in cervical ROM within or between the two groups during the 2-year follow-up period, nor was there significant difference in spinal canal enlargement between the two groups. However, both postoperative SCA and increased SCA in Group A were significantly higher than those in Group B. CONCLUSION: The contralateral open side approach is preferable to the ipsilateral open side approach in UODL for lateral cervical OPLL. LEVEL OF EVIDENCE: 3.

Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway.

Long non-coding RNAs (lncRNAs) play an important role in the development of bone-related diseases. This study was conducted to investigate the role and mechanism of lncRNA X inactive specific transcript (XIST) in the occurrence of cervical ossification of the posterior longitudinal ligament (OPLL). Here, primary human ligament fibroblasts cells (LFCs) were isolated from 30 cases of OPLL and 30 normal cervical posterior longitudinal ligament (non-OPLL) tissues to perform the qPCR and Western blot assay. We found that the mRNA level of lncRNA XIST was significantly increased in OPLL LFCs compared to non-OPLL LFCs. By bioinformatics analysis, we found that lncRNA XIST has four binding sites for miR-17-5p and found that the mRNA level of miR-17-5p was also significantly decreased in OPLL LFCs compared to non-OPLL LFCs. Since AHNAK is the target gene of miR-17-5p, we further found that the expression of AHNAK was significantly reduced in non-OPLL LFCs after being transfected with miR-17-5p mimic. The qPCR results showed that the mRNA expressions of BMP2 and Runx2 were significantly decreased. After being transfected with lncRNA XIST siRNA in the non-OPLL LFCs, the mRNA levels of lncRNA XIST, AHNAK, BMP2, and Runx2 were significantly decreased and the phosphorylated protein of Smad1/5/8 was reduced. After being cultured by mechanical vibration, the mRNA levels of lncRNA XIST, AHNAK, BMP2, Runx2, COL1, OC, OPN, and Phospho1 were significantly increased, but the mRNA expression of miR-17-5p was significantly decreased. The expression of phosphorylated Smad1/5/8 protein was also significantly increased. Together, this study was the first to determine that XIST gene inhibition plays an important role in the occurrence of cervical OPLL, through the mechanism of regulation of miR-17-5P/AHNAK/BMP2 signaling pathway. Thus, XIST may be a potential target that could be modulated for the treatment of cervical OPLL.

The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1.

Osteosarcoma(OS) is the most common and aggressive malignant bone sarcoma,which occurs in rapidly growing bones in children and adolescents. However, the underlying molecular mechanisms of OS development have not been fully illustrated. N6-Methyladenosine (m6A) is the most prevalent internal chemical modification of mRNAs, which is involved in many pathological processes in cancer development. However, its role and regulatory mechanism in OS remain unknown. In this study, we aimed to investigate the roles of m6A and its methyltransferase METTL3 in OS development. The results showed that m6A level for RNA methylation and the expression level of METTL3 were up-regulated in human OS tissues and OS cell lines. Functionally, lentivirus-mediated METTL3 silence in HOS and SAOS-2 cells inhibited the cell proliferation, migration and invasion ability. Further mechanism analysis suggested that METTL3 silence decreased the m6A methylation and total mRNA level of lymphoid enhancer-binding factor 1 (LEF1), followed by inhibited the activity of Wnt/ß-catenin signaling pathway. Moreover, LEF1 over-expression abrogates the repressive effects of METTL3 silence on the proliferation, migration and invasion abilities of OS cells. Together, these results revealed that the m6A methyltransferase METTL3 promotes osteosarcoma cell progression by regulating the m6A level of LEF1 and activating Wnt/ß-catenin signaling pathway.

WITHDRAWN: A Comparative Study Between Anterior Controllable Antedisplacement and Fusion Versus Laminoplasty in the Surgical Management of Multilevel Cervical Ossification of the Posterior Longitudinal Ligament.

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Radiographic Features and Correlation Analysis of Location of Ossification in Patients with Cervical Ossification of the Posterior Longitudinal Ligament Combined with Ossification of the Nuchal Ligament.

OBJECTIVE: To investigate the incidence, distribution characteristics, and radiographic features of the ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the nuchal ligament (ONL) and to analyze the correlation between the location of ONL and degree of ossification in patients with cervical OPLL. METHODS: From January 2010 to December 2016, the clinical data of 217 patients with cervical OPLL were reviewed retrospectively. Type and location of OPLL and ONL were determined on computed tomography images and lateral radiograph films. For patients with the local type of ONL, the segment with the largest spinal canal occupation ratio (COR) of OPLL was determined on cross-sectional computed tomography slices. The correlation between the location of ONL and segment with the largest COR of OPLL was evaluated. RESULTS: Of the 217 patients with cervical OPLL, 118 patients (54.4%) had OPLL combined with ONL (92 male and 26 female patients). The incidence of ONL was almost 1.4 times greater in males than in female patients (P = 0.03). C5-C6 (49.5%) was the segment at which ONL occurred most. Of 60 patients with the local type of ONL, 34 patients' ONL was located at the segment with largest COR of OPLL. The matching ratio was the largest (77.8%) when the type of OPLL was locally circumscribed (P = 0.003). CONCLUSIONS: The incidence of ONL was 54.4% in patients with cervical OPLL, and male patients were affected more than female patients. ONL occurred most in segment C5-C6. The location of local-type ONL commonly corresponded to the segment with the largest COR of OPLL when type of OPLL was circumscribed.

Assessment of Myelopathy in Cervical Ossification of the Posterior Longitudinal Ligament by Magnetic Resonance Imaging-Assisted 3-Dimensional Measurement.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a 3-dimensional (3D) disease that causes cervical myelopathy. The conventional 2-dimensional (2D) measurement of OPLL has limitations in estimating cord compression and myelopathy. In this study, we attempted to use 3D computed tomography (CT) and magnetic resonance imaging (MRI) to measure the 3D occupying ratio of OPLL and investigate its significance in the assessment of spinal cord myelopathy. METHODS: Three-dimensional CT and MRI were performed in 50 patients with cervical OPLL at a neutral position before surgery. MRI was done to determine the extent of spinal cord compression. The CT data were saved in DICOM format and analyzed using Mimics 17.0. Then a 3D model of OPLL was semiautomatically segmented at a specific threshold. The following data were measured: diameter of the spinal canal, thickness of the OPLL, and 3D volume of the OPLL and spinal canal. The Japanese Orthopedic Association (JOA) score was used to assess the cervical spinal cord function. RESULTS: Pearson correlation analysis showed that both the occupying ratio and the 3D occupying ratio were significantly and negatively correlated with the JOA score. Multiple linear regression analysis indicated that only the 3D occupying ratio showed a significantly negative correlation with the JOA score, whereas age, sex, and the occupying ratio were insignificantly associated with the JOA score. CONCLUSIONS: The 3D occupying ratio of OPLL is a reliable indicator for assessing the severity of spinal cord myelopathy. MRI provides more details about cord compression, making the measurement more accurate and objective.