title: Gradual strenuous running regimen predisposes to osteoarthritis due to cartilage cell death and altered levels of glycosaminoglycans.
abstract: OBJECTIVE
  To investigate the hypothesis that strenuous running is a predisposing factor for osteoarthritis.
  
  
  METHODS
  Wistar rats were divided into two groups: a control group (CG) and a trained group (TG). The TG underwent a strenuous treadmill running training regimen of controlled intensity, exhibiting progressively improvement of fitness over 12 weeks, running at least 55 km during this period and finally performing an ultra-endurance running exercise to exhaustion. After this period, rats from both groups were euthanized and their knees removed. The articular cartilage was dissected and submitted to histomorphometrical, histomorphological, and immunohistochemical analyses evaluating cell death pathway (caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)) and inflammatory cytokines [interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α)]. In addition, the tissues were analyzed regarding the types and the content of glycosaminoglycans.
  
  
  RESULTS
  The TG knee joints exhibited increase in the number of chondrocytes and chondrocyte clusters, as well as significantly increased levels of caspase-3, a protein involved in apoptosis, and of inflammatory cytokines IL-1α and TNF-α. In addition, histologically higher grades of osteoarthritis (Osteoarthritis Research Society International - OARSI grading), and significantly decreased levels of chondroitin sulfate and hyaluronic acid. Knee cartilage thickness and TUNEL did not significantly differ between the two groups.
  
  
  CONCLUSIONS
  The articular cartilage of rats subjected to a strenuous running regimen of controlled intensity exhibited molecular and histological characteristics that are present in osteoarthritis.
authors.affiliation: Department of Orthopaedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. cacarlos66@hotmail.com
authors.forename: C E S
authors.initials: CE
authors.lastname: Franciozi
authors.forename: V A F
authors.initials: VA
authors.lastname: Tarini
authors.forename: R D
authors.initials: RD
authors.lastname: Reginato
authors.forename: P R S
authors.initials: PR
authors.lastname: Gonçalves
authors.forename: V P
authors.initials: VP
authors.lastname: Medeiros
authors.forename: M
authors.initials: M
authors.lastname: Ferretti
authors.forename: J L
authors.initials: JL
authors.lastname: Dreyfuss
authors.forename: H B
authors.initials: HB
authors.lastname: Nader
authors.forename: F
authors.initials: F
authors.lastname: Faloppa
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D019902:Chondrocytes / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012420:Running; D013264:Stifle / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D004253:DNA Nucleotidylexotransferase; D053148:Caspase 3