Top

Published in:

Open Access 01-01-2012 | Original Article

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

Authors: Kenzo Uchida, Takafumi Yayama, Daisuke Sugita, Hideaki Nakajima, Alexander Rodriguez Guerrero, Shuji Watanabe, Sally Roberts, William E. Johnson, Hisatoshi Baba

Published in: European Spine Journal | Issue 1/2012

Abstract

Introduction

Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice.

Materials and methods

The mutant twy/twy mice (6 to 22-week-old) were used in the present study. The vertebral column was analyzed histologically and immunohistochemically.

Results

We observed that the enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of posterior longitudinal ligament of twy/twy mice. In this regards, the cells of the protruded hyperplastic annulus fibrosus invaded the longitudinal ligaments and induced neovascularization and metaplasia of primitive mesenchymal cells to osteoblasts in the spinal ligaments of twy/twy mice.

Conclusion

Since genetic mechanisms could play a role in human OPLL, the age-related enlargement of the nucleus pulposus in the twy/twy mouse may primarily occur as a result of overproduction of mucopolysaccharide matrix material induced by certain genetic abnormalities.

Available only for authorised users

Baba H, Furusawa N, Chen Q et al (1997) Potential role of streptozotocin in enhancing ossification of the posterior longitudinal ligament of the cervical spine in the hereditary hyperostotic mouse (twy/twy). Eur J Histochem 41:191–202PubMed

Baba H, Furusawa N, Chen Q, Imura S, Tomita K (1995) Anterior decompressive surgery for cervical ossified posterior longitudinal ligament causing myeloradiculopathy. Paraplegia 33:18–24PubMedCrossRef

Chiba K, Yamamoto I, Hirabayashi H et al (2005) Multicenter study investigating the postoperative progression of ossification of the posterior longitudinal ligament in the cervical spine: a new computer-assisted measurement. J Neurosurg Spine 3:17–23PubMedCrossRef

Furukawa K (2006) Current topics on pharmacological research on bone metabolism: molecular basis of ectopic bone formation induced by mechanical stress. J Pharmacol Sci 100:201–204PubMedCrossRef

Furusawa N, Baba H, Imura S, Fukuda M (1996) Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse. Eur J Histochem 40:199–210PubMed

Furushima K, Shimoonoda K, Maeda S et al (2002) Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res 17:128–137PubMedCrossRef

Goto S, Yamazaki M (1997) Pathogenesis of ossification of the spinal ligaments. In: Yonenobu K, Sakou T, Ono K (eds) Ossification of the posterior longitudinal ligament. Springer, Tokyo, pp 29–37

Horikoshi T, Maeda K, Kawaguchi Y et al (2006) A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Hum Genet 119:611–616PubMedCrossRef

Hosoda Y, Yoshimura Y, Higaki S (1981) A new breed of mouse showing multiple osteochondral lesions—twy mouse. Ryumachi 21:157–164PubMed

10.

Ishida Y, Kawai S (1993) Characterization of cultured cells derived from ossification of the posterior longitudinal ligament of the spine. Bone 14:85–91PubMedCrossRef

11.

Kawaguchi H, Kurokawa T, Hoshino Y, Kawahara H, Ogata E, Matsumoto T (1992) Immunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-beta in the ossification of the posterior longitudinal ligament of the cervical spine. Spine 17:33–36CrossRef

12.

Kokubun S, Sakurai M, Tanaka Y (1996) Catilaginous endplate in cervical disc herniation. Spine 21:190–195PubMedCrossRef

13.

Lipson SJ (1998) Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc. Spine 13:1055–1060CrossRef

14.

Maeda S, Ishidou S, Koga H et al (2001) Functional impact of human collagen α2 (XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res 16:948–957PubMedCrossRef

15.

Matsunaga S, Sakou T (2006) OPLL: disease entity, incidence, literature search, and prognosis. In: Yonenobu K, Nakamura K, Toyama Y (eds) OPLL, 2nd edn. Springer, Tokyo, pp 11–17CrossRef

16.

Matsunaga S, Sakou T, Taketomi E, Nakanishi K (1996) Effects of strain distribution in the intervertebral discs on the progression of ossification of the posterior longitudinal ligaments. Spine 21:184–189PubMedCrossRef

17.

Mine T, Kawai S (1995) Ultrastructural observations on the ossification of the supraspinous ligament. Spine 20:297–302PubMedCrossRef

18.

Okamoto K, Kobashi G, Washio M et al (2004) Dietary habits and risk of ossification of the posterior longitudinal ligaments of the spine (OPLL): findings from a case–control study in Japan. J Bone Miner Metab 22:612–617PubMedCrossRef

19.

Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S (1998) Mutation in Npps in a mouse model of the posterior longitudinal ligament of the spine. Nat Genet 19:271–273PubMedCrossRef

20.

Ramos-Remus C, Russell AS, Gomez-Vargas A et al (1998) Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies. Ann Rheum Dis 57:429–433PubMedCrossRef

21.

Resnick D, Guerra J Jr, Robinson CA, Vint VC (1978) Association of diffuse idiopathic skeletal hyperostosis (DISH) and calcification and ossification of the posterior longitudinal ligament. Am J Roentgenol 131:1049–1053

22.

Resnick D, Shaul SR, Robins JM (1975) Diffuse idiopathic skeletal hyperostosis (DISH): Forestier’s disease with extraspinal manifestations. Radiology 115:513–524PubMed

23.

Sakou T, Taketomi E, Matsunaga S, Yamaguchi M, Sonoda S, Yashiki S (1991) Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leucocyte antigen haplotype. Spine 16:1249–1252PubMedCrossRef

24.

Sato R, Uchida K, Kobayashi S et al (2007) Ossification of the posterior longitudinal ligament of the cervical spine: histopathological findings around the calcification and ossification front. J Neurosurg Spine 7:174–183PubMedCrossRef

25.

Seichi A, Hoshino Y, Ohnishi I, Kurokawa T (1992) The role of calcium metabolism abnormalities in the development of ossification of the posterior longitudinal ligament of the cervical spine. Spine 17:30–32CrossRef

26.

Shingyouchi Y, Nagahama A, Niida M (1996) Ligamentous ossification of the cervical spine in the late middle-aged Japanese men. Its relation to body mass index and glucose metabolism. Spine 21:2474–2478PubMedCrossRef

27.

Tanaka M, Nakahara S, Inoue H (1993) A pathologic study of discs in the elderly. Separation between the cartilaginous endplate and the vertebral body. Spine 18:1456–1462PubMed

28.

Tanno M, Furukawa KI, Ueyama K, Harata S, Motomura S (2003) Uniaxial cyclic stretch induces osteogenic differentiation and synthesis on bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone 33:475–484PubMedCrossRef

29.

Uchida K, Nakajima H, Yayama T et al (2009) High-resolution magnetic resonance imaging and 18FDG-PET findings of the cervical spinal cord before and after decompressive surgery in patients with compressive myelopathy. Spine 34:1185–1191PubMedCrossRef

30.

Watanabe K, Fishman WH (1964) Application of the stereospecific inhibitor l-phenylalanine to the enzymorphology of intestinal alkaline phosphatase. J Histochem Cytochem 12:252–260PubMedCrossRef

31.

Yamazaki M, Goto S, Kobayashi S, Terakado A, Moriya H (1994) Bone cells from spinal hyperostosis mouse (twy/twy) maintain elevated levels of collagen production in vitro. J Bone Miner Metab 12:57–63CrossRef

Title: Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)
Authors: Kenzo Uchida
Takafumi Yayama
Daisuke Sugita
Hideaki Nakajima
Alexander Rodriguez Guerrero
Shuji Watanabe
Sally Roberts
William E. Johnson
Hisatoshi Baba
Publication date: 01-01-2012
Publisher: Springer-Verlag
Published in: European Spine Journal / Issue 1/2012
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-011-1971-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

Abstract

Introduction

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2012

Epidemiological characteristics of adult SCIWORA in Tianjin, China: a preliminary study

Spinal growth modulation using a novel intravertebral epiphyseal device in an immature porcine model

Erratum to: Adult de novo lumbar scoliosis. Posterior instrumented fusion with Smith-Peterson osteotomy, decompression and management of postoperative infection

Initial experience with the use of an expandable titanium cage as a vertebral body replacement in patients with tumors of the spinal column: a report of 95 patients

Esophagus perforation complicating anterior cervical spine surgery

Modified technique for C1–2 screw-rod fixation and fusion using autogenous bicortical iliac crest graft