COL6A1, the Candidate Gene for Ossification of the Posterior Longitudinal Ligament, Is Associated With Diffuse Idiopathic Skeletal Hyperostosis in Japanese

Abstract

Because COL6A1 could be a susceptibility to the occurrence of DISH and OPLL in the Japanese population, we consider that COL6A1 could be responsible for the hyperostotic state, leading to ectopic bone formation in the spinal ligament.

High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-β1

“…The content and type of collagen directly influence the structure and property of ligaments. The potential role of collagen types in the pathogenesis of OPLL is supported by evidence from gene analysis and histopathological examination [7,23,32]. Therefore, the research on the alteration of collagen in ligament could provide a clue for the onset or progression of OPLL.…”

“…However, the implication of collagen X gene expression in these cells remains unknown although its expression was not affected by high glucose. The polymorphisms in COL6a1 gene, encoding type VI collagen, and collagen 11a2 (COL11a2) gene, encoding type XI collagen, were found to have a significantly higher prevalence in patients with OPLL than those in control subjects [23,24,32]. However, it is unknown what roles they may play in the pathology of OPLL.…”

“…Therefore, the research on the alteration of collagen in ligament could provide a clue for the onset or progression of OPLL. Since the presence of collagen types I, II, III, VI, X and XI had been confirmed in the spinal ligament of OPLL [7,30,32], all of these collagen types were examined in the present study. The main results of this study show that high glucose concentration in the culture media increases gene expression and protein synthesis of collagen types I and III, particularly, in cells of the posterior longitudinal ligament of rat cervical spine; this action mimics the effects of rh TGF-b1 on ligament cell collagen synthesis.…”

Ossification of the posterior longitudinal ligament: a review

“…120,125 Kong et al 64 studied the Han Chinese population and also found a significant association of COL6A1 with OPLL. They demonstrated that 3 single nucleotide polymorphisms, including promoter (-572T), intron 32(-29), and intron 33(+20), are significantly associated with OPLL and OLF.…”

Simultaneous ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum causing upper thoracic myelopathy in DISH: case report and literature review

“…COL6A1 is a gene that encodes the a1 chain of Type VI collagen, an extracellular matrix protein, and might provide a scaffold for osteoblastic or preosteoblastic cells or chondrocytes that subsequently proceed to membranous or endochondral ossification [27]. Because it's a susceptibility to the occurrence of DISH and OPLL in the Japanese population, COL6A1 was thought to be responsible for the hyperostotic state that led to ectopic bone formation in the spinal ligament [28]. However, no data are available to confirm this premise.…”