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Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

ABSTRACT: The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL cells were subjected to 24?hours of cyclic tensile strain. To identify differentially expressed genes associated with cyclic tensile strain, microarray analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified upregulation of various genes, particularly of the Hedgehog signaling pathway; Ihh and related genes had increased expression compared with controls after 24-hour cyclic tensile strain. In immunoblotting analysis, Ihh, Runx2, Sox9, Gli2, Gli3, and smoothened (SMO) had significantly increased expression after 6- or 12-hour cyclic tensile strain. OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, Gli2, Gli3, and SMO in the ossification front of OPLL. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and related signaling molecules, and this might be important in the ossification process in OPLL.

SUBMITTER: Sugita D

PROVIDER: S-EPMC7190672 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

Sugita Daisuke D Nakajima Hideaki H Kokubo Yasuo Y Takeura Naoto N Yayama Takafumi T Matsumine Akihiko A

Scientific reports 20200429 1

The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL ...[more]

PMID: 32350355

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Project description:BackgroundA high false-negative rate has been reported for the diagnosis of ossification of the posterior longitudinal ligament (OPLL) using plain radiography. We investigated whether deep learning (DL) can improve the diagnostic performance of radiologists for cervical OPLL using plain radiographs.Materials and methodsThe training set consisted of 915 radiographs from 207 patients diagnosed with OPLL. For the test set, we used 200 lateral cervical radiographs from 100 patients with cervical OPLL and 100 patients without OPLL. An observer performance study was conducted over two reading sessions. In the first session, we compared the diagnostic performance of the DL-model and the six observers. The diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC) at the vertebra and patient level. The sensitivity and specificity of the DL model and average observers were calculated in per-patient analysis. Subgroup analysis was performed according to the morphologic classification of OPLL. In the second session, observers evaluated the radiographs by referring to the results of the DL-model.ResultsIn the vertebra-level analysis, the DL-model showed an AUC of 0.854, which was higher than the average AUC of observers (0.826), but the difference was not significant (p = 0.292). In the patient-level analysis, the performance of the DL-model had an AUC of 0.851, and the average AUC of observers was 0.841 (p = 0.739). The patient-level sensitivity and specificity were 91% and 69% in the DL model, and 83% and 68% for the average observers, respectively. Both the DL-model and observers showed decreases in overall performance in the segmental and circumscribed types. With knowledge of the results of the DL-model, the average AUC of observers increased to 0.893 (p = 0.001) at the vertebra level and 0.911 (p < 0.001) at the patient level. In the subgroup analysis, the improvement was largest in segmental-type (AUC difference 0.087; p = 0.002).ConclusionsThe DL-based OPLL detection model can significantly improve the diagnostic performance of radiologists on cervical radiographs.

Project description:ObjectivesThe objective of this study was to quantify the morphology, composition, and asymmetry of the paravertebral extensor muscles (PSEMs) in patients with cervical ossification of the posterior longitudinal ligament (OPLL) who had different modified K-line (mK-line) and the minimum interval between the mK-line and OPLL (INTmin ) values and to investigate the relationship between PSEMs and symptoms and outcomes following laminoplasty. These original findings elucidated that the atrophy of PSEMs could predict decompression outcomes and provided a theoretical basis for paraspinal muscle rehabilitation.MethodsA total of 94 consecutive patients who underwent laminoplasty for OPLL between January 2020 and January 2022 were enrolled in this retrospective study. The relative cross-sectional areas (rCSA), functional cross-sectional areas (rFCSA), and FCSA/CSA ratio of the multifidus (MF), semispinalis cervicalis (SSCe), semispinalis capitis (SSCa), and splenius capitis (SpCa) were measured at the C3-C7 segments on cervical magnetic resonance imaging (MRI). This study compared the differences between the mK-line (+) group and the mK-line (-) group, as well as between the INTmin <4 mm group and the INTmin ≥4 mm group, using the independent t-test or Mann-Whitney test for continuous variables and the χ2 -test for categorical variables. The correlations between the PSEMs and symptoms were analyzed using either the Pearson or Spearman correlation coefficient.ResultsThe relative total CSA (rTCSA) of the PSEMs, especially the MF, was significantly smaller in the mK-line (-) group. However, the FCSA/CSA of the right deep extensor muscle (DEM) was larger. The asymmetry of the MF TFCSA/TCSA showed a significant difference between the mK-line groups. In the INTmin <4 mm group, the PSEMs rCSA and rFCSA were significantly smaller, while the bilateral MF TFCSA/TCSA and right SSCe TFCSA/TCSA were larger. The asymmetry of the superficial extensor muscle rCSA was significantly lower in the group with INTmin <4 mm. The postoperative modified Japanese Orthopedic Association score (mJOA) and mJOA recovery rate were positively correlated with the INTmin and DEM rCSA and negatively correlated with the asymmetry of MF FCSA/CSA.ConclusionsIn patients with mK-line (-) or INTmin <4 mm, the PSEMs were smaller, and the DEM atrophy and composition changes were predominant. The MF asymmetry was higher in patients with mK-lines (-), whereas the SEM atrophy and asymmetry were more prevalent in patients with INTmin <4 mm. The DEM was related to the preoperative and postoperative mJOA scores. DEM-preserving surgery or DEM-specific rehabilitation exercises can improve the recovery of patients with OPLL during the perioperative period. In addition, attention should be paid to the evaluation of the SEM, especially the SpCa at the C3 and C5 levels.

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Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

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Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

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