title: Expression of proteinases and inflammatory cytokines in subchondral bone regions in the destructive joint of rheumatoid arthritis.
abstract: OBJECTIVE
  We previously described abnormalities in the bone marrow of patients with rheumatoid arthritis (RA), but were able to shed little light on the pathogenic roles of inflammatory cytokines and proteinases in joint destruction in the subchondral region in RA. This is the first report to describe the co-localization of cytokines and proteinases in this area.
  
  
  METHODS
  Decalcified paraffin-embedded sections from 10 patients with RA and five patients with osteoarthritis (OA) were examined for the immunolocalization of cathepsins B, K and L and the localization of messenger RNAs for interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 9 (MMP-9). The cells were double-stained with anti-CD68 or anti-prolyl 4-hydroxylase (PH) antibody.
  
  
  RESULTS
  An immunohistochemical study confirmed the expression of cathepsins B and L by CD68-positive mononuclear cells at the sites of significant cartilage and bone erosion from the subchondral region in all RA specimens. Osteoclast-like cells showed intense staining for cathepsin K and MMP-9. Osteoblast-like cells strongly expressed MMP-9. Analysis of serial sections revealed that expression of the IL-1beta and TNF-alpha genes occurred near that of the cathepsins and MMP-9 in the subchondral region.
  
  
  CONCLUSIONS
  We conclude that inflammatory cytokines and tissue-damaging proteinases play important roles in joint destruction in the subchondral region in RA.
authors: Department of Orthopaedic Surgery, Osaka University Medical School, Osaka, Japan.
authors: M
authors: M
authors: Kaneko
authors: T
authors: T
authors: Tomita
authors: T
authors: T
authors: Nakase
authors: Y
authors: Y
authors: Ohsawa
authors: H
authors: H
authors: Seki
authors: E
authors: E
authors: Takeuchi
authors: H
authors: H
authors: Takano
authors: K
authors: K
authors: Shi
authors: K
authors: K
authors: Takahi
authors: E
authors: E
authors: Kominami
authors: Y
authors: Y
authors: Uchiyama
authors: H
authors: H
authors: Yoshikawa
authors: T
authors: T
authors: Ochi
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007596:Joints / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002403:Cathepsins; D010450:Endopeptidases; D020780:Matrix Metalloproteinase 9