title: Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model.
abstract: OBJECTIVE
  The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate markers of functional impairment in relation to cartilage loss and pathological changes in a post-traumatic mouse model of OA.
  
  
  METHODS
  We performed a battery of functional analyses in a mouse model of OA generated by cruciate ligament transection (CLT). The changes in functional analyses were linked to histological changes graded by OARSI standards, histological grading of synovitis, and volumetric changes of the articular cartilage and osteophytes quantified by phase contrast micro-computed tomography (μCT).
  
  
  RESULTS
  OA generated by CLT led to decreased time on rotarod, delayed response on hotplate analysis, and altered gait starting from 4 weeks after surgery. Activity in open field analysis did not change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was directly correlated with higher OARSI histological scores of OA, synovitis in the knee joints, cartilage volume loss, and osteophyte formation.
  
  
  CONCLUSIONS
  Our findings link functional analyses to histological grading, synovitis, comprehensive three-dimensional assessment of cartilage volume and osteophyte formation. This serves as a reference for a mouse model in predicting outcomes of OA treatment.
authors: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. ruan@bcm.edu
authors: M Z C
authors: MZ
authors: Ruan
authors: R M
authors: RM
authors: Patel
authors: B C
authors: BC
authors: Dawson
authors: M-M
authors: MM
authors: Jiang
authors: B H L
authors: BH
authors: Lee
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000473:pathology / Q000503:physiopathology; D000070598:Anterior Cruciate Ligament Injuries; D018771:Arthralgia / Q000175:diagnosis / Q000503:physiopathology*; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D005684:Gait / Q000502:physiology*; D007718:Knee Injuries / Q000473:pathology / Q000503:physiopathology; D007719:Knee Joint / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000503:physiopathology*; D054850:Osteophyte / Q000473:pathology / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology; D011930:Reaction Time / Q000502:physiology
keywords: Animal models; Cartilage volume quantification; Functional analysis; Gait; Motor; Osteoarthritis; Osteophyte; Pain; Synovitis
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