title: Initiation of degenerative joint damage by experimental bleeding combined with loading of the joint: a possible mechanism of hemophilic arthropathy.
abstract: OBJECTIVE
  To investigate the effect of a limited number of experimental joint bleedings, combined with loading of the affected joint, on the development of progressive degenerative joint damage.
  
  
  METHODS
  The right knee of 8 mature beagle dogs was injected with freshly collected autologous blood 3 times per week for 4 weeks, to mimic a limited number of joint hemorrhages occurring over a short period. To ensure loading of the experimental joint, the contralateral control knee of the animals was fixed to the trunk 4 hours per day, 3 days per week. Ten weeks after the last injection, cartilage tissue and synovium were collected from both knees to analyze features of joint degeneration. Cartilage was prepared for analysis of proteoglycan turnover (synthesis, retention, release, and content) and histologic features. Synovium was prepared for histologic analysis.
  
  
  RESULTS
  The rate of proteoglycan synthesis was significantly increased, characteristic of degenerative cartilage damage as seen in osteoarthritis. Release of newly formed proteoglycans (as a measure of retention) and total loss of proteoglycans from the cartilage matrix were increased. Cartilage matrix integrity was adversely altered, as shown by histologic damage. Histologic analysis also revealed signs of synovial inflammation. These effects were not observed 10 weeks after the experimental bleedings in joints that did not undergo forced loading.
  
  
  CONCLUSIONS
  Experimental joint bleedings when combined with loading of the affected joint resulted in features of progressive degenerative joint damage, whereas similar joint hemorrhages without joint loading did not. This might reflect a possible mechanism of joint damage in hemophilia.
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michel J J
authors.initials: MJ
authors.lastname: Hooiveld
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.forename: Kim M G
authors.initials: KM
authors.lastname: Jacobs
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Vianen
authors.forename: H Marijke
authors.initials: HM
authors.lastname: van den Berg
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000818:Animals; D019902:Chondrocytes / Q000473:pathology; D004285:Dogs; D006467:Hemophilia A / Q000473:pathology* / Q000503:physiopathology*; D006470:Hemorrhage / Q000473:pathology*; D007596:Joints / Q000473:pathology* / Q000503:physiopathology; D015203:Reproducibility of Results; D013583:Synovial Membrane / Q000473:pathology*; D016474:Weight-Bearing