title: Cyclic loading increases friction and changes cartilage surface integrity in lubricin-mutant mouse knees.
abstract: OBJECTIVE
  To investigate the effects of lubricin gene dosage and cyclic loading on whole joint coefficient of friction and articular cartilage surface integrity in mouse knee joints.
  
  
  METHODS
  Joints from mice with 2 (Prg4(+/+)), 1 (Prg4(+/-)), or no (Prg4(-/-)) functioning lubricin alleles were subjected to 26 hours of cyclic loading using a custom-built pendulum. Coefficient of friction values were measured at multiple time points. Contralateral control joints were left unloaded. Following testing, joints were examined for histologic evidence of damage and cell viability.
  
  
  RESULTS
  At baseline, the coefficient of friction values in Prg4(-/-) mice were significantly higher than those in Prg4(+/+) and Prg4(+/-) mice (P < 0.001). Cyclic loading continuously increased the coefficient of friction in Prg4(-/-) mouse joints. In contrast, Prg4(+/-) and Prg4(+/+) mouse joints had no coefficient of friction increases during the first 4 hours of loading. After 26 hours of loading, joints from all genotypes had increased coefficient of friction values compared to baseline and unloaded controls. Significantly greater increases occurred in Prg4(-/-) and Prg4(+/-) mouse joints compared to Prg4(+/+) mouse joints. The coefficient of friction values were not significantly associated with histologic evidence of damage or loss of cell viability.
  
  
  CONCLUSIONS
  Our findings indicate that mice lacking lubricin have increased baseline coefficient of friction values and are not protected against further increases caused by loading. Prg4(+/-) mice are indistinguishable from Prg4(+/+) mice at baseline, but have significantly greater coefficient of friction values following 26 hours of loading. Lubricin dosage affects joint properties during loading, and may have clinical implications in patients for whom injury or illness alters lubricin abundance.
authors: Alpert Medical School of Brown University, Rhode Island Hospital Providence, Rhode Island 02903, USA.
authors: Elizabeth I
authors: EI
authors: Drewniak
authors: Gregory D
authors: GD
authors: Jay
authors: Braden C
authors: BC
authors: Fleming
authors: Ling
authors: L
authors: Zhang
authors: Matthew L
authors: ML
authors: Warman
authors: Joseph J
authors: JJ
authors: Crisco
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D017276:Friction / Q000502:physiology*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology*; D000099158:Proteoglycan 4
chemical_list: D011509:Proteoglycans; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4