Biologic Modification of Ligamentum Flavum Cells by Marker Gene Transfer and Recombinant Human Bone Morphogenetic Protein-2

Moon, Seong Hwan; Park, Seung Rim; Kim, Hyang; Kwon, Un Hye; Kim, Keong Hee; Kim, Hak-Sun; Lee, Hwan Mo

doi:10.1097/00007632-200405010-00003

Cited by 19 publications

(12 citation statements)

References 19 publications

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“…BMP-2 promotes osteogenic differentiation, the matrix production and proliferation of spinal ligament cells both in the OPLL and in some non-OPLL cell lines, but stimulating effects on the OPLL cells are more significant [26,47]. Treatment with BMP-2 or adenovirus-mediated BMP-2 cDNA gene transfer, results in up-regulation of the expression of osteogenic phenotypes and bone nodule formation in human ligamentum flavum cells [59]. Therefore, BMP-2 may act as both an initiator and a promoter of the ossification.…”

Section: Bmpsmentioning

confidence: 99%

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Jiang

Dai

2007

Eur Spine J

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Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-beta (TGF-beta), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL.

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Section: Bmpsmentioning

confidence: 99%

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Jiang

Dai

2007

Eur Spine J

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“…Recombinant BMP-2 has been shown to enhance the osteoblastic characteristics of osteoblast-like cells, as well as ligament cells from the posterior longitudinal ligament and ligamentum flavum. [32][33][34][35][36] Histopathological studies have also found significant increase in expression of BMP-2 in the ossification area of OLF and OPLL. [37][38][39][40] So we next specifically focus on BMP-2 variants in TOLF patients.…”

Section: Discussionmentioning

confidence: 97%

Two novel BMP-2 variants identified in patients with thoracic ossification of the ligamentum flavum

Chen

Fan

et al. 2017

Eur J Hum Genet

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Thoracic ossification of the ligamentum flavum (TOLF)is a common cause of thoracic spinal canal stenosis and has been reported almost exclusively in East Asian countries. In this study, we established a relationship between bone morphogenic protein 2 (BMP-2) and TOLF. We divided patients into two groups according to severity of ossification and identified susceptible loci through exome sequencing. We identified 39 novel likely pathogenic variants in 29 genes in the transforming growth factor-beta (TGF-β) superfamily or TGF-β/BMPs signaling pathway, including two missense variants in BMP-2 (NM_001200.3) exon region, c.460C>G:p.(R154G) and c.584G>T:p.(R195M). Further Sanger sequencing and genotyping suggested the variants were only found in patients with long regional OLF. Bioinformatic assays predicted the two BMP-2 variants to cause significant alterations to gene and protein expression. Functional assays showed upregulation of BMP-2 expression, increased osteogenic marker expression, and enhanced osteogenic differentiation. Collectively, these results suggest a genetic contribution to the pathogenesis of TOLF, particularly in patients with long segment disease, and that nucleotide substitutions associated with increased BMP-2 expression may be involved in TOLF pathogenesis.

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“…14 Many authors have postulated that it derives broadly from mechanical stress, but other metabolic and genetic factors may also be of relevance. 3,10,11,[27][28][29][30][31][32] Histologically, the lesion often presents with degeneration and disorganization of elastic fibers. 12,25,26,33,34 Yoshida et al 33 and Yayama et al 12 have shown increased production of collagen fibers in the lesion.…”

Section: Discussionmentioning

confidence: 99%

Compressive Myelopathy Due to Ossification of the Ligamentum Flavum: Case Report and Review of the Literature

et al. 2017

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Ossification of the ligamentum flavum (OLF) is a rare condition in which the ligamentum flavum, due to mechanical, biological and genetic factors, becomes ossified. Due to its nature and anatomic location, OLF produces symptoms characteristic of spinal cord compression. The diagnostic confirmation is based primarily on imaging tests such as computed tomography (CT) and magnetic resonance imaging (MRI). Ossification of the ligamentum flavum most often affects Asian populations, rarely occurring in black people. The authors report a case of a 61-year-old black man with progressive paraparesis due to OLF, and review the literature regarding the pathology's prevalence, pathogenesis, clinical features, diagnosis, treatment and prognosis.

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Biologic Modification of Ligamentum Flavum Cells by Marker Gene Transfer and Recombinant Human Bone Morphogenetic Protein-2

Cited by 19 publications

References 19 publications

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Two novel BMP-2 variants identified in patients with thoracic ossification of the ligamentum flavum

Compressive Myelopathy Due to Ossification of the Ligamentum Flavum: Case Report and Review of the Literature

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