Genetic Mapping of Ossification of the Posterior Longitudinal Ligament of the Spine

Koga, Hiroaki; Sakou, Takashi; Taketomi, Eiji; Hayashi, Kyoji; Numasawa, Takuya; Harata, Seiko; Yone, Kazunori; Matsunaga, Shunji; Otterud, Brith; Inoue, Ituro; Leppert, M.

doi:10.1086/301868

Cited by 147 publications

(99 citation statements)

References 28 publications

(30 reference statements)

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“…It is unclear why thoracic myelopathy more often develops in middleaged people compared to cervical myelopathy patients. OLF and OPLL, the major causes of thoracic myelopathy, might be associated with some genetic factors (Koga et al 1998;Yamamoto et al 2002). The thoracic spine is naturally kyphotic and the spinal cord runs anterior of the spinal canal, which suggests the cord is more easily damaged from the anterior side.…”

Section: Discussionmentioning

confidence: 99%

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

Aizawa

Sato²,

Tanaka

et al. 2006

Tohoku J. Exp. Med.

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E., NISHIHIRA T. and KOKUBUN, S. Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15Years. Tohoku J. Exp. Med., 210 (3),[199][200][201][202][203][204][205][206][207][208] Thoracic myelopathy is defined as spinal cord compression in the thoracic region, leading to sensory and motor dysfunctions in the trunk and lower extremities, and can be caused by various degenerative processes of the spine. Thoracic myelopathy is rare, and there are many unsolved problems including its epidemiological and clinical features. We have established a registration system of spinal surgeries, which covered almost all surgeries in Miyagi Prefecture, and enrolled the data of 265 patients with thoracic myelopathy from 1988 to 2002. The annual rate of surgery gradually increased and averaged 0.9 per 100,000 inhabitants, which was less than 1/10 of that for cervical myelopathy. About 20 patients with thoracic myelopathy are operated on in Miyagi Prefecture each year. It frequently develops in middle-aged males. About half of the cases were caused by ossification of the ligamentum flavum, followed by ossification of the posterior longitudinal ligament, intervertebral disc herniation and posterior spur. Patients usually noticed numbness or pain in the legs and the preoperative duration was long, averaging 2 years. Its symptomatic similarities to lumbar disorders might cause difficulty in making a correct diagnosis. Since thoracic myelopathy can markedly restrict the activities of daily life, even general physicians should recognize this entity. thoracic myelopathy; epidemiological study; ossification of the ligamentum flavum; ossification of the posterior longitudinal ligament

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Section: Discussionmentioning

confidence: 99%

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

Aizawa

Sato²,

Tanaka

et al. 2006

Tohoku J. Exp. Med.

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“…Many collagen genes have been studied, including human collagen a2 gene (COL11A2). Koga et al 61 showed that this gene, located on chromosome 6p close to the human leukocyte antigen region, is strongly associated with OPLL. Retaining exon 7 together with removal of exon 6 observed in intron 6(-4A) in the COL11A2 gene could play a protective role in the ectopic ossification process.…”

Section: Pathogenesismentioning

confidence: 99%

Ossification of the posterior longitudinal ligament: a review

Saetia

Cho

Lee

et al. 2011

FOC

122

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Ossification of the posterior longitudinal ligament (OPLL) is most commonly found in men, the elderly, and Asian patients. There are many diseases associated with OPLL, such as diffuse idiopathic skeletal hyperostosis, ankylosing spondylitis, and other spondyloarthropathies. Several factors have been reported to be associated with OPLL formation and progression, including genetic, hormonal, environmental, and lifestyle factors. However, the pathogenesis of OPLL is still unclear. Most symptomatic patients with OPLL present with neurological deficits such as myelopathy, radiculopathy, and/or bowel and bladder symptoms. There are some reports of asymptomatic OPLL. Both static and dynamic factors are related to the development of myelopathy. Plain radiography, CT, and MR imaging are used to evaluate OPLL extension and the area of spinal cord compression. Management of OPLL continues to be controversial. Each surgical technique has some advantages and disadvantages, and the choice of operation should be made case by case, depending on the patient's condition, level of pathology, type of OPLL, and the surgeon's experience. In this paper, the authors attempt to review the incidence, pathology, pathogenesis, natural history, clinical presentation, classification, radiological evaluation, and management of OPLL.

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“…OPLL patients show ectopic bone formation in the posterior longitudinal ligament, which compresses the spinal cord leading to various neurological symptoms. Despite the late onset (average age of onset is 50 years), OPLL has a strong genetic background as shown in classical epidemiological studies and by an estimate of relative risk to siblings of ϳ10 (2,3). Because genetic factors appear to play crucial roles in the etiology of OPLL, genetic screenings to identify susceptibility are important.…”

mentioning

confidence: 99%

The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1

Ikeda

Yoshida

Tsukahara

et al. 2005

Journal of Biological Chemistry

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Ossification of the posterior longitudinal ligament of the spine (OPLL) is the leading cause of myelopathy in Japan and is diagnosed by ectopic bone formation in the paravertebral ligament. OPLL is a systemic high bone mass disease with a strong genetic background. To detect genes relevant to the pathogenesis of OPLL, we performed a cDNA microarray analysis of systematic gene expression profiles during the osteoblastic differentiation of ligament cells from OPLL patients (OPLL cells), patients with a disorder called ossification of yellow ligament (OYL), and non-OPLL controls together with human mesenchymal stem cells (hMSCs) after stimulating them with osteogenic differentiation medium (OS). Twenty-four genes were up-regulated during osteoblastic differentiation in OPLL cells. Zinc finger protein 145 (promyelotic leukemia zinc finger or PLZF) was one of the highly expressed genes during osteoblastic differentiation in all the cells examined. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of hMSCs and C2C12 cells. Small interfering RNA-mediated gene silencing of PLZF resulted in a reduction in the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1 (Col1a1), Runx2/core-binding factor 1 (Cbfa1), and osteocalcin genes, even in the presence of OS in hMSCs. The expression of PLZF was unaffected by the addition of bone morphogenetic protein 2 (BMP-2), and the expression of BMP-2 was not affected by PLZF in hMSCs. In C2C12 cells, overexpression of PLZF increased the expression of Cbfa1 and Col1a1; on the other hand, the overexpression of CBFA1 did not affect the expression of Plzf. These findings indicate that PLZF plays important roles in early osteoblastic differentiation as an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients.Ossification of the posterior longitudinal ligament of the spine (OPLL) 1 is a common hyperostotic disorder among Japanese and other Asian populations with a prevalence of 2-4% of the general population (1). OPLL patients show ectopic bone formation in the posterior longitudinal ligament, which compresses the spinal cord leading to various neurological symptoms. Despite the late onset (average age of onset is 50 years), OPLL has a strong genetic background as shown in classical epidemiological studies and by an estimate of relative risk to siblings of ϳ10 (2, 3). Because genetic factors appear to play crucial roles in the etiology of OPLL, genetic screenings to identify susceptibility are important. To date, we have performed genetic linkage and linkage disequilibrium studies to identify the causalities of OPLL and have successfully identified collagen 11A2 (COL11A2) and collagen 6A1 (3-6). We also demonstrated that an intron 6 (Ϫ4a) polymorphism of COL11A2 affects the splicing of exon 6 in ligament cells from OPLL patients (5). Although the identification of genetic factors of OPLL has important implications, the overall picture of the molecul...

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Genetic Mapping of Ossification of the Posterior Longitudinal Ligament of the Spine

Cited by 147 publications

References 28 publications

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

Ossification of the posterior longitudinal ligament: a review

The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1

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