title: Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis.
abstract: OBJECTIVE
  Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA.
  
  
  METHODS
  Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0-1) cartilage samples. Chondrocyte nuclei were stained with propidium iodide, examined by fluorescence microscopy, and the findings were recorded in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index) and were correlated with the OA grade and the surface cell densities.
  
  
  RESULTS
  In grade 2 cartilage samples, superficial chondrocytes were situated in horizontal patterns, such as strings, clusters, pairs, and singles, comparable to the patterns in nondegenerative cartilage. In intact cartilage samples from grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in 2 parallel lines, building double strings. These double strings correlated significantly with an increased number of chondrocytes per group and an increased corresponding superficial zone cell density. They were observed in all grade 2 condyles and some grade 2 tibiae, but never in grade 0-1 cartilage.
  
  
  CONCLUSIONS
  This study is the first to identify a distinct spatial reorganization of human superficial chondrocytes in response to distant early OA lesions, suggesting that proliferation had occurred distant from focal early OA lesions. This spatial reorganization may serve to recruit metabolically active units as an attempt to repair focal damage.
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA. berndrolauffs@gogglemail.com
authors.forename: Bernd
authors.initials: B
authors.lastname: Rolauffs
authors.forename: James M
authors.initials: JM
authors.lastname: Williams
authors.forename: Matthias
authors.initials: M
authors.lastname: Aurich
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Kuettner
authors.forename: Ada A
authors.initials: AA
authors.lastname: Cole
mesh_terms: D002358:Cartilage, Articular / Q000473:pathology* / Q000502:physiology; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D019902:Chondrocytes / Q000473:pathology* / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007719:Knee Joint / Q000473:pathology* / Q000503:physiopathology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000503:physiopathology