title: Immunohistochemical demonstration of advanced glycation end products and the effects of advanced glycation end products in ossified ligament tissues in vitro.
abstract: METHODS
  This study correlates advanced glycation end products with ossified ligament tissues of the cervical spine in vitro.
  
  
  OBJECTIVE
  To investigate the effect of advanced glycation end products on ossification of the spinal ligaments in vitro.
  
  
  BACKGROUND
  We have hypothesized that an accumulation of advanced glycation end products in the spinal ligament might result in some observable change in specific growth factors responsible for ossification in the spinal ligaments.
  
  
  METHODS
  Samples of the posterior longitudinal and yellow ligaments were harvested from patients (n = 5) with ossification of the posterior longitudinal ligament, and analyzed for the presence of advanced glycation end products and their receptor advanced glycation end product receptor by immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to quantify the messenger ribonucleic acid (mRNA) levels of bone morphogenetic protein (BMP)-2, BMP-7, alkaline phosphatase, an osteoblast-specific transcription factor 1 (Cbfa1), and osteocalcin from yellow ligament cells treated with advanced glycation end products.
  
  
  RESULTS
  Immunohistochemical analysis revealed that advanced glycation end products and advanced glycation end product receptor were localized to within the posterior longitudinal and yellow ligaments. Advanced glycation end products were found to increase significantly the expression of BMP-2, BMP-7, Cbfa1, and osteocalcin at the mRNA levels after treatment with advanced glycation end products (1 microg/mL).
  
  
  CONCLUSIONS
  This is the first report to investigate the correlation, if any, between the ossified spinal ligament and advanced glycation end products. These results suggested that accumulation in advanced glycation end products and their interaction with advanced glycation end product receptor were 1 of the important risk factors in the process of ossification in the spinal ligaments.
authors.affiliation: Department of Orthopedic Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Yokosuka
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Kotaro
authors.initials: K
authors.lastname: Jimbo
authors.forename: Tatuhiro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kei
authors.initials: K
authors.lastname: Yamada
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Sato
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Kensei
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002574:Cervical Vertebrae; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008022:Ligaments / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000378:metabolism* / Q000473:pathology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013904:Thoracic Vertebrae; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D000469:Alkaline Phosphatase