title: Onset of preclinical osteoarthritis: the angular spatial organization permits early diagnosis.
abstract: OBJECTIVE
  Superficial articular chondrocytes display distinct spatial remodeling processes in response to the onset of distant osteoarthritis (OA). Such processes may be used to diagnose early events before manifest OA results in tissue destruction and clinical symptoms. Using a novel method of spatial quantification by calculating the angles between a chondrocyte and its surrounding neighbors, we compared maturational and degenerative changes of the cellular organizations in rat and human cartilage specimens.
  
  
  METHODS
  The nuclei of superficial chondrocytes obtained from intact rat cartilage and from human knee cartilage, as well as from cartilage with focal and severe OA, were digitally recorded in top-down views. Their Cartesian coordinates were used to determine the nearest neighbor for each chondrocyte and the angle between these 2 cells and a reference. These angles, cellularity, nearest neighbor distances, and aggregation were analyzed as a function of location and OA severity.
  
  
  RESULTS
  Neighboring rat chondrocytes exhibited intricate angular patterns with 4 dominant angles that were maintained during maturation and during the onset and progression of OA. Within intact cartilage, human chondrocytes demonstrated 1 dominant angle and, thus, a significantly different angular organization. With early OA onset, human chondrocytes that were located within intact cartilage displayed an increased occurrence of 4 angles; the resulting angular patterns were indistinguishable from those observed in rats. The angular remodeling was associated with location- and OA severity-dependent changes in cellularity and aggregation.
  
  
  CONCLUSIONS
  This study is the first to identify the presence of angular characteristics of spatial chondrocyte organization and species-specific remodeling processes correlating with OA onset. The appearance of distinct angular and spatial patterns between neighboring chondrocytes can identify the onset of distant OA prior to microscopically visible tissue damage and possibly before clinical onset. With further development, this novel concept may become suitable for the diagnosis and followup of patients susceptible to OA.
authors.affiliation: Trauma Center, Eberhard Karls University, Tuebingen, Germany. berndrolauffs@googlemail.com
authors.forename: Bernd
authors.initials: B
authors.lastname: Rolauffs
authors.forename: Miriam
authors.initials: M
authors.lastname: Rothdiener
authors.forename: Christian
authors.initials: C
authors.lastname: Bahrs
authors.forename: Andreas
authors.initials: A
authors.lastname: Badke
authors.forename: Kuno
authors.initials: K
authors.lastname: Weise
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Kuettner
authors.forename: Bodo
authors.initials: B
authors.lastname: Kurz
authors.forename: Matthias
authors.initials: M
authors.lastname: Aurich
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: Wilhelm K
authors.initials: WK
authors.lastname: Aicher
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D007596:Joints / Q000473:pathology; D008875:Middle Aged; D010003:Osteoarthritis / Q000175:diagnosis* / Q000473:pathology; D051381:Rats; D012720:Severity of Illness Index