title: Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka Shimoaizuki 23-3, Eiheiji, Fukui, 910-1193, Japan. kuchida@u-fukui.ac.jp
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uchida
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugita
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Alexander
authors.initials: A
authors.lastname: Rodriguez Guerrero
authors.forename: Shuji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
authors.forename: William E
authors.initials: WE
authors.lastname: Johnson
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D000818:Animals; D002574:Cervical Vertebrae / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009999:Ossification, Heterotopic / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology