Bone mineral density in patients with ossification of the posterior longitudinal ligament in the cervical spine

Yamauchi, Tsuneto; Taketomi, Eiji; Matsunaga, Shunji; Sakou, Takashi

doi:10.1007/s007740050098

Cited by 42 publications

(24 citation statements)

References 10 publications

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“…These results suggest that there should be distinct pathways of osteoblastic differentiation mediated by OS and BMP-2, respectively. DISCUSSION A bone loss disease, osteoporosis, is the opposite of OPLL and, indeed, has been observed in OPLL patients at low frequency compared with subjects of similar ages (34). Therefore, elucidation of the molecular etiology of OPLL might permit us to develop novel therapeutic tools for osteoporosis as well.…”

Section: Effect Of Plzf On the Expression Of Cbfa1 And Vice Versa-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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Section: Effect Of Plzf On the Expression Of Cbfa1 And Vice Versa-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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“…Several studies have investigated the relationship between OPLL and bone and mineral metabolism [8][9][10][11][12][13]. Matsui et al [8] demonstrated the presence of increased serum procollagen type I carboxyl-terminal peptide and intact osteocalcin in patients with OPLL.…”

Section: Introductionmentioning

confidence: 98%

Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine

et al. 2015

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Sclerostin and dickkopf-1(DKK1) are Wnt/β-catenin signal antagonists that play an important role in bone formation. Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by pathological ectopic ossification of the posterior longitudinal ligament and ankylosing spinal hyperostosis. The aims of this study were to evaluate serum sclerostin and DKK1 levels in persons with OPLL and to identify its relationship with bone metabolism and bone mass in persons with OPLL. This was a case-control study, and 78 patients with OPLL were compared with 39 age- and sex-matched volunteers without OPLL. We analyzed the relationship with calciotropic hormones, bone turnover markers, OPLL localization, number of ossified vertebrae, and bone mineral density of total hip (TH-BMD). Serum sclerostin levels in men with OPLL were significantly higher than in men in the control group (control group: mean = 45.3 pmol/L; OPLL group: mean = 75.7 pmol/L; P = 0.002). Age and sclerostin levels were positively correlated in men with OPLL (r = 0.43; P = 0.002). Serum sclerostin levels in men with OPLL had a positive correlation with TH-BMD Z-score (r = 0.511; P = 0.011, n = 30). There was a strong negative correlation between serum sclerostin levels and serum DKK1 levels in men with OPLL (r = -0.506; P < 0.001). Bone and mineral metabolism in OPLL differs between men and women. In men with OPLL, systemic secretion of sclerostin increases with advancing age and with higher bone mass. These two Wnt/β-catenin signal antagonists have the opposite effect in persons with OPLL, and higher serum sclerostin levels are counterbalanced by underproduction of DKK1.

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“…In several studies, patients with OPLL had higher BMD than the non-OPLL controls, 34,73,134 but BMD may decrease in patients with advancing OPLL. 87 Aita et al 2 studied histomorphometry of the iliac bone in patients with OPLL and found no significant differences between OPLL and control groups.…”

mentioning

confidence: 97%

Ossification of the posterior longitudinal ligament: a review

Saetia

Cho

Lee

et al. 2011

FOC

119

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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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Bone mineral density in patients with ossification of the posterior longitudinal ligament in the cervical spine

Cited by 42 publications

References 10 publications

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

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

Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine

Ossification of the posterior longitudinal ligament: a review

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