title: Cellularity and cartilage matrix increased in hypertrophied ligamentum flavum: histopathological analysis focusing on the mechanical stress and bone morphogenetic protein signaling.
abstract: METHODS
  Histopathological and immunohistochemical analysis.
  
  
  OBJECTIVE
  To investigate the histological changes and expression of bone morphogenetic protein (BMP) signaling component in hypertrophied ligamentum flavum (LF), and to clarify the effect of mechanical stress on them.
  
  
  BACKGROUND
  Hypertrophic changes of the LF are a major factor in degenerative lumbar canal stenosis (DLCS), but their mechanism remains unclear. BMPs are growth factors that regulate many cellular processes including proliferation, differentiation, and extracellular matrix synthesis. However, a few studies have investigated the expressions of BMP signaling in the hypertrophied LF.
  
  
  METHODS
  A total of 133 LF specimens from patients with DLCS and 17 control LF specimens from patients with lumbar disc herniation were analyzed histologically using hematoxylin and eosin, elastica van Gieson, and toluidine blue staining. To analyze the influence of mechanical stress, the DLCS specimens were divided into 2 groups: DLCS with and DLCS without hypermobility groups. The LF thickness was measured by magnetic resonance image, and the correlations between the thickness and the histological data were analyzed. Immunohistochemical analyses were carried out to confirm the expressions and localizations of BMP signaling components.
  
  
  RESULTS
  The cell number and cartilage matrix area were significantly increased in the hypertrophied LF, and those changes were more obvious in DLCS with hypermobility than in DLCS without hypermobility. The cellularity and percentage of cartilage matrix area had positive linear correlations with the LF thickness. BMP receptors and BMP ligands were both expressed by many cells of the hypertrophied LF, and some of these cells were positive for Sox9, CD105, and Msx2. The percentage of immunopositive cells for each BMP receptor type was significantly higher in DLCS with hypermobility than in DLCS without hypermobility.
  
  
  CONCLUSIONS
  Higher cellularity and increased cartilage matrix area are important changes in LF hypertrophy. These results suggest that BMP signaling and mechanical stress may play a role in the hypertrophied LF.
authors: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Najibullah
authors: N
authors: Shafaq
authors: Akinobu
authors: A
authors: Suzuki
authors: Hidetomi
authors: H
authors: Terai
authors: Shigeyuki
authors: S
authors: Wakitani
authors: Hiroaki
authors: H
authors: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology*; D017843:Ligamentum Flavum / Q000378:metabolism / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D013130:Spinal Stenosis / Q000378:metabolism / Q000473:pathology*; D013314:Stress, Mechanical
chemical_list: D019485:Bone Morphogenetic Proteins