title: Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model.
abstract: OBJECTIVE
  To investigate the longitudinal angiogenic activity of subchondral bone and cartilage during the progression of osteoarthritis (OA) using a rabbit model of OA.
  
  
  METHODS
  OA was surgically induced by anterior cruciate ligament transaction (ACLT) in left knee of 12 months old female New Zealand white rabbits (n = 33). Histological examination, immunohistochemistry, and angiogenic activity assay was done at 0, 2, 4, 6, 8, 12 weeks after ACLT. Histologic evaluation was performed with haematoxylin and eosin, safranin-O staining to assess the OA change of medial femoral condyle (MFC) and lateral femoral condyle (LFC). CD31 immunohistochemistry was performed to confirm the vascular invasion at osteochondral junction. A co-cultured tubule formation assay was conducted to evaluate angiogenic activity of the subchondral bone and cartilage of MFC and LFC as well as synovium. Association between histological changes, angiogenic activity, and vascular invasion were evaluated.
  
  
  RESULTS
  OA changes increased in a time-dependent manner both in MFC and LFC. Angiogenic activity of subchondral bone showed a monomodal change during the OA progression, achieved a peak in the early to progressive stage and decreased to normal level in the late stage of OA. Surge of vascular invasion was observed following the increase of angiogenic activity in the progressive stage of OA. Angiogenic activity of cartilage did not change during the course of OA progression.
  
  
  CONCLUSIONS
  Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Sasho
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Ikegawa
authors.forename: R
authors.initials: R
authors.lastname: Akagi
authors.forename: Y
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: S
authors.initials: S
authors.lastname: Mukoyama
authors.forename: N
authors.initials: N
authors.lastname: Ochiai
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: A
authors.initials: A
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery*; D001169:Arthritis, Experimental / Q000473:pathology*; D002358:Cartilage, Articular / Q000098:blood supply*; D018450:Disease Progression; D005260:Female; D005269:Femur / Q000098:blood supply* / Q000473:pathology; D007150:Immunohistochemistry; D007719:Knee Joint / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020370:Osteoarthritis, Knee / Q000473:pathology*; D011817:Rabbits