The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

Yan, Liang; Gao, Rui; Liu, Yang; He, Baorong; Lv, Shemin; Hao, Dingjun

doi:10.14336/ad.2017.0201

Cited by 79 publications

(77 citation statements)

References 100 publications

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“…Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder that is characterized by progressive ectopic bone formation in the PLL. OPLL mainly occurs in the cervical spine (70%) and can result in various degrees of neurological symptoms, ranging from local pain to severe myelopathy due to the compression of the spinal cord and nerve roots by increasingly calcified PLL tissues (Yan et al, 2017). So far, there is a lack of effective drug therapy against OPLL.…”

Section: Introductionmentioning

confidence: 99%

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells

Dong

Yuan

et al. 2020

Cell Biology International

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Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf‐1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non‐OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/β‐catenin signaling, as indicated by stabilized β‐catenin and increased T‐cell factor‐dependent transcriptional activity. Functionally, Dkk1 exerts a growth‐inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2‐induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.

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Section: Introductionmentioning

confidence: 99%

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells

Dong

Yuan

et al. 2020

Cell Biology International

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“…The ossification consumes the space reserve of the spinal canal through a very slow process. So patients with severe cervical OPLL can possess zero symptoms before fierce deterioration after mild triggers 5 . The disease can be easily misdiagnosed as cervical spondylotic myelopathy but should be dealt with more cautions 6 .…”

Section: Introductionmentioning

confidence: 99%

Multilevel Anterior Cervical Corpectomy and Fusion for Ossification of the Posterior Longitudinal Ligament

Zhang

Chen

Huang

et al. 2020

Preprint

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Background Cervical ossification of the posterior longitudinal ligament (OPLL) is a kind of spinal disorder widely spared in Asia. In dealing with multilevel cervical OPLL, the ideal surgical approach is still under debate. Here we introduce our findings of multilevel anterior cervical corpectomy and fusion (ACCF) in treating multilevel cervical OPLLMethods 79 patients with multilevel cervical OPLL who had ACOR on C4-C5 or C5-C6 were retrospectively reviewed. Patients’ Japanese Orthopedic Association (JOA) Score, the improvement rate of JOA Scores (RIS), sagittal cervical mobility (SCM) and the distance between the lower endplate of the vertebra body above the titanium mesh and the superior endplate of the vertebra body below the titanium mesh ( L ) were analyzed and subjected into paired-t test. Radiographic features and complications were described as well.Results p<0.001 in all paired-t tests of JOA Scores, SCM and L at 1day, 6months, 1year and 2year follow-ups compared with preoperative ones. Patients’ RIS continued to increase in 2 years. 6 (7.59%) patients’ L at the 2 years follow-up shortened more than 10mm than their postoperative L. 1 (1.27%) patient had severe titanium mesh canting.Conclusions Multilevel ACCF procedure has positive outcomes in treating multilevel cervical OPLL. Postoperative complications like titanium subsidence and dislocation can happen after this procedure. Follow-ups should be conducted regularly and thoroughly with this kind of patients.

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“…Ossi cation of the posterior longitudinal ligament (OPLL) is characterized by heterotopic ossi cation in the spine ligament [1,2]. At present, several genetic and non-genetic factors are involved in the pathological progress of OPLL.…”

Section: Introductionmentioning

confidence: 99%

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament

Yang

Lin

Chen

et al. 2020

Preprint

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Background: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy associated gene expression was correlated with the expression of osteogenic differentiation genes. Methods: Expression of autophagy associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson’s correlation. The expression of autophagy associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative Polymerase Chain Reaction (RT-qPCR), western blotting and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. Results: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r=0.8233, P<0.001), alkaline phosphatase, biomineralization associated (ALP) (r=0.7821, P<0.001) and collagen type 1 (COL 1) (r=0.6078, P=0.001). Consistently, the upregulation of autophagy associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP and COL 1 by 63.2% (P<0.01), 52% (P<0.01) and 53.2% (P<0.01) in ligament fibroblasts from patients with OPLL, respectively. Conclusions: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts, and promoted the development of OPLL.

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The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

Cited by 79 publications

References 100 publications

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells

Multilevel Anterior Cervical Corpectomy and Fusion for Ossification of the Posterior Longitudinal Ligament

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament

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