title: Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study.
abstract: OBJECTIVE
  In osteoarthritis (OA), changes occur in both cartilage and subchondral bone. The subchondral bone plate facilitates normal cross-talk between articular cartilage and trabecular subchondral bone, and adaptive changes in the plate due to OA may therefore disturb cross-talk homeostasis. To investigate these changes over time, we examined the cartilage-subchondral bone interface using a combined approach of histologic analysis and in vivo microfocal computed tomography.
  
  
  METHODS
  Sixteen-week-old male C57BL/6 mice (n=32) received intraarticular injections of collagenase in 1 joint to induce instability-related OA and received saline injections in the contralateral knee joint (control joint). At 2, 4, 6, 10, and 14 weeks after injection, changes in the tibial subchondral bone plate and subchondral trabeculae were analyzed.
  
  
  RESULTS
  Two weeks after injection, collagenase-injected joints had significantly more cartilage damage and osteophytosis than did control joints. Osteoclast activity directly underneath the subchondral bone plate was significantly elevated in collagenase-injected joints compared to control joints (mean±SEM osteoclast surface/bone surface 11.07±0.79% versus 7.60±0.81%), causing the plate to become thinner and creating a large increase in subchondral bone plate porosity (mean±SEM cumulative porosity volume 0.05±0.04×10(-3) mm3 in control joints versus 2.52±0.69×10(-3) mm3 in collagenase-injected joints). Four weeks after injection, the previously formed perforations disappeared, coinciding with a significant rise in osteoblast activity in the subchondral trabecular bone in collagenase-injected joints compared to control joints (mean ± SEM bone formation rate/bone surface 0.62±0.13 μm3/μm2 per day versus 0.30±0.03 μm3/μm2 per day).
  
  
  CONCLUSIONS
  The current study is the first to provide quantitative longitudinal data on the dynamic changes in the subchondral bone plate after OA induction. The development of plate perforations may enhance mutual interaction between subchondral trabeculae, bone marrow cells, and the articular cartilage in OA.
authors.affiliation: Erasmus Medical Center, Department of Internal Medicine, Rotterdam, The Netherlands.
authors.forename: Sander M
authors.initials: SM
authors.lastname: Botter
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: Stefan
authors.initials: S
authors.lastname: Clockaerts
authors.forename: Jan H
authors.initials: JH
authors.lastname: Waarsing
authors.forename: Harrie
authors.initials: H
authors.lastname: Weinans
authors.forename: Johannes P T M
authors.initials: JP
authors.lastname: van Leeuwen
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000473:pathology; D017364:Collagenases; D004195:Disease Models, Animal; D007719:Knee Joint / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D051379:Mice; D010003:Osteoarthritis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D011859:Radiography; D013977:Tibia / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D017364:Collagenases