Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients

Wei, Wenbin; He, Hailong; Chen, C. Y.; Zhao, Yanfang; Jiang, Huling; Liu, W. T.; Du, Zhenfang; Chen, X. L.; Shi, Shu-Yue; Zhang, X. N.

doi:10.4238/2014.march.17.7

Cited by 21 publications

(15 citation statements)

References 35 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent study showed that the incidence rate of OPLL has reach more than 5% in some of the Asian regions outside Japan 21 . The disease also increases with age, with the average onset age of around 50 years old, and the male to female ratio at 2:1 22 . Despite advances in surgery and radiographic technologies, treating OPLL is still a task that has not been improved.…”

Section: Discussionmentioning

confidence: 99%

“…Beside non-genetic factors like mechanical stress, nutrition, glucose intolerance, and high body mass index, recent studies showed numerous genes are associated with the disease. Most of these genes are vital to the ossification process like NPPS, COL11A2, COL6A1, BMP2, BMP4, TGF-β1, TGF-β3 4 5 6 7 22 24 , and often aberrant expression of these genes can cause the pathological heterogeneous ossification 25 26 . This means a certain disorder in the upstream regulatory network of these critical factors may exists during the pathological process of OPLL.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Chen

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Ossification of the posterior longitudinal ligament (OPLL) is a genetic disorder which involves pathological heterotopic ossification of the spinal ligaments. Although studies have identified several genes that correlated with OPLL, the underlying regulation network is far from clear. Through small RNA sequencing, we compared the microRNA expressions of primary posterior longitudinal ligament cells form OPLL patients with normal patients (PLL) and identified 218 dysregulated miRNAs (FDR < 0.01). Furthermore, assessing the miRNA profiling data of multiple cell types, we found these dysregulated miRNAs were mostly OPLL specific. In order to decipher the regulation network of these OPLL specific miRNAs, we integrated mRNA expression profiling data with miRNA sequencing data. Through computational approaches, we showed the pivotal roles of these OPLL specific miRNAs in heterotopic ossification of longitudinal ligament by discovering highly correlated miRNA/mRNA pairs that associated with skeletal system development, collagen fibril organization, and extracellular matrix organization. The results of which provide strong evidence that the miRNA regulatory networks we established may indeed play vital roles in OPLL onset and progression. To date, this is the first systematic analysis of the micronome in OPLL, and thus may provide valuable resources in finding novel treatment and diagnostic targets of OPLL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Chen

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Mutations and/or aberrant expressions of collagen genes may induce various pathological phenotypes in connective tissues. Many collagen genes are shown to be associated with OPLL, including COL11A2 ,[ 31 - 34 ] COL6A1 [ 20 , 35 - 37 ] and collagen 17A1 ( COL17A1 ) [ 38 ]. COL11A2 is the type XI collagen that associates with type II collagen, the main collagenous component of cartilage.…”

Section: Opll Susceptibility Genes and Signalingmentioning

confidence: 99%

“…Three different SNPs of COL6A1 have been found to be associated with OPLL: promoter (-572T), intron 32(-29) and intron 33 (+20) [ 20 , 35 - 37 ]. Wei et al have found two SNPs of COL17A1 , rs805698 (c.G1282A, p.G428S) and rs4918079 (c.C2595T, p.R865R), are significantly associated with OPLL via a whole exome sequencing [ 38 ]. The specific roles of these SNPs of collagen genes in the pathogenesis of OPLL remain unclear, though their contributions to the formation of extracellular matrix scaffolds may facilitate endochondral ossification.…”

Section: Opll Susceptibility Genes and Signalingmentioning

confidence: 99%

The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

Yan

Gao²,

Liu

et al. 2017

Aging and disease

View full text Add to dashboard Cite

Ossification of the posterior longitudinal ligament (OPLL) is a multi-factorial disease involving an ectopic bone formation of spinal ligaments. It affects 0.8-3.0% aging Asian and 0.1-1.7% aging European Caucasian. The ossified ligament compresses nerve roots in the spinal cord and causes serious neurological problems such as myelopathy and radiculopathy. Research in understanding pathogenesis of OPLL over the past several decades have revealed many genetic and non-genetic factors contributing to the development and progress of OPLL. The characterizations of aberrant signaling of bone morphogenetic protein (BMP) and mitogen-activated protein kinases (MAPK), and the pathological phenotypes of OPLL-derived mesenchymal stem cells (MSCs) have provided new insights on the molecular mechanisms underlying OPLL. This paper reviews the recent progress in understanding the pathophysiology of OPLL and proposes future research directions on OPLL.

show abstract

“…The pathogenesis of OPLL remains unclear, and genetic factors are considered to play a predominant role in the development of cervical OPLL (C-OPLL) (11,12). To date, more than 10 susceptibility genes/loci have been shown to be associated with susceptibility to C-OPLL (10,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). However, few studies have assessed the contribution of T-OPLL susceptibility genes.…”

Section: Introductionmentioning

confidence: 99%

The COL6A1 rs201153092 single nucleotide polymorphism, associates with thoracic ossification of the posterior longitudinal ligament

et al. 2019

View full text Add to dashboard Cite

Thoracic ossification of the posterior longitudinal ligament (T-OPLL) is one of the most common factors that causes thoracic spinal stenosis, resulting in intractable myelopathy and radiculopathy. Our previous study reported that the rs201153092 polymorphism present in the collagen 6A1 (COL6A1) gene was a potentially pathogenic locus for the development of T-OPLL. The present study aimed to determine whether the rs201153092 mutation causes abnormal expression of COL6A1 in Han Chinese patients with T-OPLL, and to examine the effects of this mutation on osteogenesis by establishing a model of osteogenic differentiation. COL6A1 gene mutant and wild-type mouse 3T3-E1 embryonic osteoblast models were constructed to induce the differentiation of these cells into osteoblasts. The potential of the mutation site to induce abnormal expression of the COL6A1 gene and osteogenic markers was assessed via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that the rs201153092A mutation site resulted in significantly increased COL6A1 gene expression levels in the OPLL tissues obtained following clinical surgery. This mutation was shown to play an important role in the development of T-OPLL by regulating the overexpression of the COL6A1 gene and significantly increasing the expression levels of osteogenic markers. The findings of the present study suggested that the rs201153092A mutant variant could increase the expression levels of COL6A1 and consequently play a role in the pathogenesis of T-OPLL.

show abstract

Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients

Cited by 21 publications

References 35 publications

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

The COL6A1 rs201153092 single nucleotide polymorphism, associates with thoracic ossification of the posterior longitudinal ligament

Contact Info

Product

Resources

About