title: Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis.
abstract: OBJECTIVE
  To examine the histopathological changes in spinal tissues of ankylosing spondylitis (AS) patients.
  
  
  METHODS
  Tissue samples from 10 AS patients and 10 control subjects were obtained. Hematoxylin and eosin, picrosirius, Masson and van Gieson stainings were utilized to determine the pathological changes in tissues. Ultrastructural alterations were examined by electronic microscopy. Proteoglycan levels were assessed by enzyme-linked immunosorbent assays (ELISA). Matrix metalloproteinase-3 (MMP-3), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) levels were evaluated by immunohistochemistry.
  
  
  RESULTS
  Our results demonstrate that the density of collagen fibrils was reduced in the supraspinous ligaments of AS tissue and fibrils were loosely and irregularly organized as compared to a regular distribution of collagen fibrils in controls. In ligamentum flava from AS patients, activated fibroblasts with enlarged nuclei were detected, while the number of elastic fibers was greatly decreased. Paraspinal muscle tissues of AS patients exhibited increased collagen fibril accumulation and atrophy. Significantly decreased proteoglycan and elevated MMP-3 levels were found in supraspinous ligament samples from AS patients (P < 0.01). Additionally, the levels of TGF-β1 in ligamentum flava and paraspinal muscle tissues of AS patients were increased (P < 0.01). The expression of TNF-α was also upregulated in the ligamentum flavum (P < 0.01), with no significant difference in the paraspinal muscle between control and AS patients (P > 0.05).
  
  
  CONCLUSIONS
  Our findings reveal histopathological changes that occur in certain spinal tissues of AS patients and suggest that increased levels of MMP-3 and TGF-β1 may contribute to the pathogenesis of AS.
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Tongwei
authors.initials: T
authors.lastname: Chu
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D017843:Ligamentum Flavum / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D008875:Middle Aged; D064170:Paraspinal Muscles / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D011509:Proteoglycans / Q000032:analysis; D013167:Spondylitis, Ankylosing / Q000201:enzymology / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D011509:Proteoglycans; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: MMP-3; TGF-β1; ankylosing spondylitis (AS); collagen fibril; histopathology