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Osteoarthritis Cartilage. 2014 Oct;22(10):1461-9. doi: 10.1016/j.joca.2014.07.011.

In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis.

Author information

1
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.
2
Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA. Electronic address: mjanderson@ucdavis.edu.
3
Biomedical Engineering Graduate Group, University of California-Davis, USA; Department of Pharmacology, University of California-Davis Medical Center, USA. Electronic address: ndejesus@ucdavis.edu.
4
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.
5
Biomedical Engineering Graduate Group, University of California-Davis, USA; Department of Pharmacology, University of California-Davis Medical Center, USA. Electronic address: cripplinger@ucdavis.edu.
6
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.

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.

DESIGN:

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.

KEYWORDS:

Bone resorption; Cathepsin; Fluorescence reflectance imaging; Inflammation; Post-traumatic osteoarthritis; Protease

PMID:
25278057
PMCID:
PMC4185155
DOI:
10.1016/j.joca.2014.07.011
[Indexed for MEDLINE]
Free PMC Article

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