title: Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis.
abstract: OBJECTIVE
  Chondromodulin-I (ChM-I), a cartilage derived anti-angiogenic factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage.
  
  
  METHODS
  Expression of ChM-I, type II collagen, basic fibroblast growth factor, vascular endothelial growth factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA.
  
  
  RESULTS
  Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-angiogenic markers, and decreased expression of ChM-I.
  
  
  CONCLUSIONS
  High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-angiogenic factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.
authors.affiliation: Department of Orthopedic Surgery, Niigata University School of Medicine (NUSM), Niigata, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hayami
authors.forename: Haruko
authors.initials: H
authors.lastname: Funaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yaoeda
authors.forename: Kaori
authors.initials: K
authors.lastname: Mitui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamagiwa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatano
authors.forename: Jun
authors.initials: J
authors.lastname: Kondo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Le T
authors.initials: LT
authors.lastname: Duong
authors.forename: Naoto
authors.initials: N
authors.lastname: Endo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002358:Cartilage, Articular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D024043:Collagen Type II / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D006614:Hindlimb; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013264:Stifle / Q000473:pathology* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; C489407:Cnmd protein, rat; D024043:Collagen Type II; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D020780:Matrix Metalloproteinase 9