title: Histological changes in chronic autoimmune SKG-arthritis evaluated by quantitative three-dimensional stereological estimators.
abstract: OBJECTIVE
  To investigate the quantitative arthritic and bone erosive changes, including the number of osteoclasts and osteoclast precursors in the new SKG-model of inflammatory polyarthritis using three-dimensional (3D) stereological methods.
  
  
  METHODS
  Arthritis was induced in female SKG-mice with Zymosan A. Quantitative histology was made in four control mice and four mice with arthritis euthanised after 6 and 12 weeks. The right hind paw was embedded undecalcified in methylmethacrylate and cut exhaustively generating vertical uniform random sections. A computer controlled microscope and stereological software was used for histological quantification. Total volumes were estimated according to the Cavalieri principle, total surfaces were estimated using the vertical sections design, and the number of osteoclasts was counted in a physical fractionator.
  
  
  RESULTS
  The arthritis score increased during the 12-week period and was paralleled by an increase in the volume of inflammatory tissue (r=0.96, p<0.001). The number of osteoclasts on bone (r=0.77, p<0.05) and osteoclast-covered bone surface (r=0.62, p<0.05) increased resulting in a decrease in the volume of bone (r=-0.65, p<0.05). However, the number of osteoclast precursors declined between week 6 and 12 (p<0.05). Furthermore, the total cartilage surface (r=-0.74, p<0.05) and cartilage volume (r=-0.74, p<0.05) decreased during the 12 weeks of arthritis.
  
  
  CONCLUSIONS
  In this study we demonstrated changes in 3D stereological parameters of inflammatory tissue, bone erosion, osteoclasts, and cartilage in mouse paws during the course of arthritis in the SKG mouse. This is the first time 3D quantitative histology has been applied in a mouse model of rheumatoid arthritis.
authors: Department of Rheumatology, Aarhus University Hospital, Aarhus Denmark. kresten@hotmail.com
authors: K K
authors: KK
authors: Keller
authors: Kr
authors: K
authors: Stengaard-Pedersen
authors: F
authors: F
authors: Dagnæs-Hansen
authors: J R
authors: JR
authors: Nyengaard
authors: S
authors: S
authors: Sakaguchi
authors: E-M
authors: EM
authors: Hauge
mesh_terms: D000818:Animals; D001168:Arthritis / Q000473:pathology*; D001327:Autoimmune Diseases / Q000473:pathology*; D002356:Cartilage / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D016591:Histocytological Preparation Techniques / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000473:pathology