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OPLL  -  ossification of posterior longitudinal...

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Disease relevance of OPLL

  • OPLL is a common disorder among elderly populations in eastern Asia and is the leading cause of spinal myelopathy in Japan. We performed a genomewide linkage study with 142 affected sib pairs, to identify genetic loci related to OPLL [1].
  • Ossification of the posterior longitudinal ligament (OPLL) of the spine is a subset of "bone-forming" diseases, characterized by ectopic ossification in the spinal ligaments [1].
  • PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) is a common, well-recognized cause of spinal stenosis and myelopathy in Japan. Although also common in whites, especially among the elderly, it has received little scientific attention [2].
  • To start screening for the molecular variants of RXR beta in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXR beta and elucidated the genomic organization of the gene [3].
  • OPLL was reported in 15 (29%, 95% CI 17, 41) patients (nine AS, two psoriatic arthritis, three juvenile AS, and one Reiter's syndrome) [4].

Psychiatry related information on OPLL

  • Whether the similar dietary habits play an important role in the high prevalence of OPLL in Taiwan was of interest [5].
  • However, there is little information about the relationship between OPLL and life styles in the prime of life (between 30 and 50 years) [6].
  • METHODS: To facilitate early prediction and prevention of OPLL, we analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol drinking and hangover in subjects in the prime of life [6].

High impact information on OPLL

  • In multipoint linkage analysis using GENEHUNTER-PLUS, evidence of linkage to OPLL was detected on chromosomes 1p, 6p, 11q, 14q, 16q, and 21q [1].
  • Identification of the locus of susceptibility to OPLL by genomewide linkage and linkage disequilibrium studies permits us to investigate the pathogenesis of the disease, which may lead to the development of novel therapeutic tools [1].
  • Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL [7].
  • 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 [8].
  • Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients [9].

Chemical compound and disease context of OPLL

  • It is concluded that OPLL of the cervical spine is an unexpectedly prevalent cause of myelopathy among patients treated in the United States. Thin-section axial CT metrizamide myelography with small interslice intervals is essential for the investigation of patients who may have OPLL [10].
  • The patient subsequently had acute quadriplegia develop, with the ensuing MRI study illustrating severe spinal stenosis at the C5, C6 level as a result of OPLL or a large extruded disc herniation [11].
  • This paper describes 8 Italian patients with cervical spine stenosis due to OPLL extending three to five vertebral segments (and above C3 in four cases) [12].
  • Twelve cases, including cervical trauma, cervical spondylosis, and ossification of the posterior longitudinal ligament (OPLL), underwent multilevel corpectomies or spondylectomies with iliac bone or hydroxylapatite grafting combined with the TLSP system [13].
  • STUDY DESIGN: This work was performed to investigate the role of vitamin K (VK) in the pathogenesis of ossification of posterior longitudinal ligament (OPLL), by analyzing the biochemical markers of the blood samples of OPLL patients and responses of ligament cells derived from OPLL lesion to VK2 [14].

Biological context of OPLL


Anatomical context of OPLL

  • Similar mRNA species were observed in undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal ligament of non-OPLL subjects [17].
  • Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord [15].
  • A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification [15].
  • OPLL was demonstrated as a low-signal-intensity band between the bone marrow of the vertebral body and the dural sac on T1- and T2-weighted images [18].
  • In contrast, cell lines (OG1-OG5) obtained from an OPLL patient showed several different phenotypic characteristics for osteoblasts [19].

Associations of OPLL with chemical compounds

  • Cyclic stretch induced an increase in PGI2 synthase in OPLL cells in a time-dependent manner, whereas no change was observed in non-OPLL cells [20].
  • A stretch-activated Ca(2+) channel blocker, Gd(3+), the voltage-dependent L-type Ca(2+) channel blockers diltiazem and nifedipine, and Ca(2+)-free medium suppressed stretch-induced ALP activity, which suggests a role of Ca(2+) influx in the signal transduction of mechanical stress to the osteogenic response of OPLL cells [21].
  • The mRNA expressions of Cbfa1 (an osteoblast-specific transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells [22].
  • CONCLUSION: Proton-density sagittal and axial images are important in establishing the diagnosis of OPLL [23].
  • Medial corpectomy, C5 to C7, and removal of OPLL, with subsequent fusion C4 to T1 using a free fibula graft resulted in clinical improvement [24].

Regulatory relationships of OPLL

  • Exogenous TGF-beta inhibited proliferation in the OPLL cells but promoted proliferation in control cells [25].

Other interactions of OPLL

  • These results indicate that the genetic causality of OPLL lies within or close to the RXR beta/COL11A2 locus [3].
  • RESEARCH QUESTIONS: (a) Is any clinical variable of ankylosing spondylitis (AS) associated with the presence of ossification of the posterior longitudinal ligament (OPLL)? and (b) Is OPLL present in patients with AS from different geographical or genetic backgrounds [4]?
  • TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL [26].
  • The positive expression of BMP and TGF-beta in HPLL cells of myelopathic patients, and their similarity to OPLL, suggest that these cells have the potential to differentiate into osteogenic cells [27].
  • The Zucker fatty rat, another animal model for OPLL, has a missense mutation in the leptin receptor gene [28].

Analytical, diagnostic and therapeutic context of OPLL

  • Two variants in the intergenic region, 3' end + 140 and 3' end + 561, exhibit statistically significant associations with OPLL in case-control study (p = 0.0028 for 3' end + 140 and p = 0.034 for 3' end + 561) [3].
  • OPLL was observed in two of the control group [4].
  • To identify the genes related to ossification affected by mechanical stress during OPLL, analyses using cDNA microarray were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching [29].
  • However, incidence of a fracture-dislocation through a solid multilevel anterior cervical discectomy and fusion (ACDF) construct with no associated underlying pathology of AS, DISH, or OPLL but severe osteopenia has not, to the best knowledge of the authors, been reported in the medical literature [30].
  • Although surgical decompression of the involved spinal cord achieves a good recovery of neurological conditions, one of the most important complaints of patients with ossification of the posterior longitudinal ligament (OPLL) is disability as a result of spinal immobility [31].


  1. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Tanaka, T., Ikari, K., Furushima, K., Okada, A., Tanaka, H., Furukawa, K., Yoshida, K., Ikeda, T., Ikegawa, S., Hunt, S.C., Takeda, J., Toh, S., Harata, S., Nakajima, T., Inoue, I. Am. J. Hum. Genet. (2003) [Pubmed]
  2. Diagnosis and treatment of ossification of the posterior longitudinal ligament of the spine: report of eight cases and literature review. Trojan, D.A., Pouchot, J., Pokrupa, R., Ford, R.M., Adamsbaum, C., Hill, R.O., Esdaile, J.M. Am. J. Med. (1992) [Pubmed]
  3. Human retinoic X receptor beta: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine. Numasawa, T., Koga, H., Ueyama, K., Maeda, S., Sakou, T., Harata, S., Leppert, M., Inoue, I. J. Bone Miner. Res. (1999) [Pubmed]
  4. Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies. Ramos-Remus, C., Russell, A.S., Gomez-Vargas, A., Hernandez-Chavez, A., Maksymowych, W.P., Gamez-Nava, J.I., Gonzalez-Lopez, L., García-Hernández, A., Meoño-Morales, E., Burgos-Vargas, R., Suarez-Almazor, M.E. Ann. Rheum. Dis. (1998) [Pubmed]
  5. Ossification of the posterior longitudinal ligament of the spine. A case-control risk factor study. Wang, P.N., Chen, S.S., Liu, H.C., Fuh, J.L., Kuo, B.I., Wang, S.J. Spine. (1999) [Pubmed]
  6. Sleeping habit and other life styles in the prime of life and risk for ossification of the posterior longitudinal ligament of the spine (OPLL): a case-control study in Japan. Washio, M., Kobashi, G., Okamoto, K., Sasaki, S., Yokoyama, T., Miyake, Y., Sakamoto, N., Ohta, K., Inaba, Y., Tanaka, H. Journal of epidemiology / Japan Epidemiological Association. (2004) [Pubmed]
  7. Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Koga, H., Sakou, T., Taketomi, E., Hayashi, K., Numasawa, T., Harata, S., Yone, K., Matsunaga, S., Otterud, B., Inoue, I., Leppert, M. Am. J. Hum. Genet. (1998) [Pubmed]
  8. The promyelotic leukemia zinc finger promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1. Ikeda, R., Yoshida, K., Tsukahara, S., Sakamoto, Y., Tanaka, H., Furukawa, K., Inoue, I. J. Biol. Chem. (2005) [Pubmed]
  9. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. Yonemori, K., Imamura, T., Ishidou, Y., Okano, T., Matsunaga, S., Yoshida, H., Kato, M., Sampath, T.K., Miyazono, K., ten Dijke, P., Sakou, T. Am. J. Pathol. (1997) [Pubmed]
  10. Cervical spine stenosis secondary to ossification of the posterior longitudinal ligament. Harsh, G.R., Sypert, G.W., Weinstein, P.R., Ross, D.A., Wilson, C.B. J. Neurosurg. (1987) [Pubmed]
  11. Acute quadriplegia following closed traction reduction of a cervical facet dislocation in the setting of ossification of the posterior longitudinal ligament: case report. Wimberley, D.W., Vaccaro, A.R., Goyal, N., Harrop, J.S., Anderson, D.G., Albert, T.J., Hilibrand, A.S. Spine. (2005) [Pubmed]
  12. Cervical spine stenosis due to ossification of the posterior longitudinal ligament in Italian patients: surgical treatment and outcome. Maiuri, F., Iaconetta, G., Gambardella, A., Buonamassa, S. Archives of orthopaedic and trauma surgery. (2000) [Pubmed]
  13. Anterior cervical fixation with the titanium locking screw-plate: a preliminary report. Tominaga, T., Koshu, K., Mizoi, K., Yoshimoto, T. Surgical neurology. (1994) [Pubmed]
  14. High serum levels of menatetrenone in male patients with ossification of the posterior longitudinal ligament. Yamada, K., Inui, K., Iwamoto, M., Nakamura, H., Tsujio, T., Konishi, S., Ito, Y., Takaoka, K., Koike, T. Spine. (2003) [Pubmed]
  15. Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine. Koshizuka, Y., Kawaguchi, H., Ogata, N., Ikeda, T., Mabuchi, A., Seichi, A., Nakamura, Y., Nakamura, K., Ikegawa, S. J. Bone Miner. Res. (2002) [Pubmed]
  16. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Nakamura, I., Ikegawa, S., Okawa, A., Okuda, S., Koshizuka, Y., Kawaguchi, H., Nakamura, K., Koyama, T., Goto, S., Toguchida, J., Matsushita, M., Ochi, T., Takaoka, K., Nakamura, Y. Hum. Genet. (1999) [Pubmed]
  17. Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine. Maeda, S., Ishidou, Y., Koga, H., Taketomi, E., Ikari, K., Komiya, S., Takeda, J., Sakou, T., Inoue, I. J. Bone Miner. Res. (2001) [Pubmed]
  18. Spinal cord compression due to ossification of ligaments: MR imaging. Yamashita, Y., Takahashi, M., Matsuno, Y., Sakamoto, Y., Yoshizumi, K., Oguni, T., Kojima, R. Radiology. (1990) [Pubmed]
  19. Characterization of cultured cells derived from ossification of the posterior longitudinal ligament of the spine. Ishida, Y., Kawai, S. Bone (1993) [Pubmed]
  20. Role of prostaglandin I2 in the gene expression induced by mechanical stress in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Ohishi, H., Furukawa, K., Iwasaki, K., Ueyama, K., Okada, A., Motomura, S., Harata, S., Toh, S. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  21. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Tanno, M., Furukawa, K.I., Ueyama, K., Harata, S., Motomura, S. Bone (2003) [Pubmed]
  22. Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Iwasaki, K., Furukawa, K.I., Tanno, M., Kusumi, T., Ueyama, K., Tanaka, M., Kudo, H., Toh, S., Harata, S., Motomura, S. Calcif. Tissue Int. (2004) [Pubmed]
  23. Ossification of the posterior longitudinal ligament: MR evaluation. Otake, S., Matsuo, M., Nishizawa, S., Sano, A., Kuroda, Y. AJNR. American journal of neuroradiology. (1992) [Pubmed]
  24. Cervical myelopathy secondary to ossification of the posterior longitudinal ligament in a Caucasian patient. Maroun, F.B., Makino, A.P., Tong, T.R., Perkins, P.G., Arts, R., Jacob, J.C., Reddy, R. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. (1993) [Pubmed]
  25. Effect of transforming growth factor-beta on fibroblasts in ossification of the posterior longitudinal ligament. Inaba, K., Matsunaga, S., Ishidou, Y., Imamura, T., Yoshida, H. In Vivo (1996) [Pubmed]
  26. A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Horikoshi, T., Maeda, K., Kawaguchi, Y., Chiba, K., Mori, K., Koshizuka, Y., Hirabayashi, S., Sugimori, K., Matsumoto, M., Kawaguchi, H., Takahashi, M., Inoue, H., Kimura, T., Matsusue, Y., Inoue, I., Baba, H., Nakamura, K., Ikegawa, S. Hum. Genet. (2006) [Pubmed]
  27. Immunohistochemistry of symptomatic hypertrophy of the posterior longitudinal ligament with special reference to ligamentous ossification. Song, J., Mizuno, J., Hashizume, Y., Nakagawa, H. Spinal Cord (2006) [Pubmed]
  28. The extent of ossification of posterior longitudinal ligament of the spine associated with nucleotide pyrophosphatase gene and leptin receptor gene polymorphisms. Tahara, M., Aiba, A., Yamazaki, M., Ikeda, Y., Goto, S., Moriya, H., Okawa, A. Spine. (2005) [Pubmed]
  29. Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Iwasawa, T., Iwasaki, K., Sawada, T., Okada, A., Ueyama, K., Motomura, S., Harata, S., Inoue, I., Toh, S., Furukawa, K.I. Calcif. Tissue Int. (2006) [Pubmed]
  30. Traumatic fracture-dislocation of C5 on C6 through a previously solid multilevel anterior cervical discectomy and fusion: a case report and review of the literature. Orndorff, D.G., Samartzis, D., Whitehill, R., Shen, F.H. The spine journal : official journal of the North American Spine Society. (2006) [Pubmed]
  31. Bath ankylosing spondylitis functional index (BASFI) evaluation of postoperative patients with OPLL. Mori, K., Hukuda, S., Katsuura, A., Saruhashi, Y., Matsusue, Y. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. (2004) [Pubmed]
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