title: In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis.
abstract: OBJECTIVE
  Joint injuries initiate a surge of inflammatory cytokines and proteases that contribute to cartilage and subchondral bone degeneration. Detecting these early processes in animal models of post-traumatic osteoarthritis (PTOA) typically involves ex vivo analysis of blood serum or synovial fluid biomarkers, or histological analysis of the joint. In this study, we used in vivo fluorescence reflectance imaging (FRI) to quantify protease, matrix metalloproteinase (MMP), and Cathepsin K activity in mice following anterior cruciate ligament (ACL) rupture. We hypothesized that these processes would be elevated at early time points following joint injury, but would return to control levels at later time points.
  
  
  METHODS
  Mice were injured via tibial compression overload, and FRI was performed at time points from 1 to 56 days after injury using commercially available activatable fluorescent tracers to quantify protease, MMP, and cathepsin K activity in injured vs uninjured knees. PTOA was assessed at 56 days post-injury using micro-computed tomography and whole-joint histology.
  
  
  RESULTS
  Protease activity, MMP activity, and cathepsin K activity were all significantly increased in injured knees relative to uninjured knees at all time points, peaking at 1-7 days post-injury, then decreasing at later time points while still remaining elevated relative to controls.
  
  
  CONCLUSIONS
  This study establishes FRI as a reliable method for in vivo quantification of early biological processes in a translatable mouse model of PTOA, and provides crucial information about the time course of inflammation and biological activity following joint injury. These data may inform future studies aimed at targeting these early processes to inhibit PTOA development.
authors.affiliation: Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA; Biomedical Engineering Graduate Group, University of California-Davis, USA. Electronic address: psatkun@ucdavis.edu.
authors.forename: P B
authors.initials: PB
authors.lastname: Satkunananthan
authors.affiliation: Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA. Electronic address: mjanderson@ucdavis.edu.
authors.forename: M J
authors.initials: MJ
authors.lastname: Anderson
authors.affiliation: Biomedical Engineering Graduate Group, University of California-Davis, USA; Department of Pharmacology, University of California-Davis Medical Center, USA. Electronic address: ndejesus@ucdavis.edu.
authors.forename: N M
authors.initials: NM
authors.lastname: De Jesus
authors.affiliation: Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA; Biomedical Engineering Graduate Group, University of California-Davis, USA. Electronic address: drhaudenschild@ucdavis.edu.
authors.forename: D R
authors.initials: DR
authors.lastname: Haudenschild
authors.affiliation: Biomedical Engineering Graduate Group, University of California-Davis, USA; Department of Pharmacology, University of California-Davis Medical Center, USA. Electronic address: cripplinger@ucdavis.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Ripplinger
authors.affiliation: Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA; Biomedical Engineering Graduate Group, University of California-Davis, USA. Electronic address: bchristiansen@ucdavis.edu.
authors.forename: B A
authors.initials: BA
authors.lastname: Christiansen
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001862:Bone Resorption / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology*; D056657:Cathepsin K / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007718:Knee Injuries / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging; D061848:Optical Imaging; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D010447:Peptide Hydrolases; D056657:Cathepsin K; D020782:Matrix Metalloproteinases
keywords: Bone resorption; Cathepsin; Fluorescence reflectance imaging; Inflammation; Post-traumatic osteoarthritis; Protease