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

Autor: P. B. Satkunananthan, N. M. De Jesus, Crystal M. Ripplinger, Dominik R. Haudenschild, Matthew J. Anderson, Blaine A. Christiansen
Rok vydání: 2014
Předmět:
Cartilage
Articular
Male
Aging
Pathology
Knee Joint
Cathepsin K
Bone resorption
Osteoarthritis
Fluorescence reflectance imaging
Mice
Blood serum
2.1 Biological and endogenous factors
Medicine
Orthopedics and Sports Medicine
Aetiology
Optical Imaging
Osteoarthritis
Knee
Molecular Imaging
medicine.anatomical_structure
Female
medicine.medical_specialty
Proteases
Physical Injury - Accidents and Adverse Effects
Post-traumatic osteoarthritis
Anterior cruciate ligament
Clinical Sciences
Biomedical Engineering
Knee Injuries
Article
Cathepsin
Rheumatology
Animals
Synovial fluid
Knee
Inflammation
Animal
business.industry
Anterior Cruciate Ligament Injuries
Cartilage
X-Ray Microtomography
Human Movement and Sports Sciences
medicine.disease
Matrix Metalloproteinases
Arthritis & Rheumatology
Protease
Disease Models
Animal
Musculoskeletal
Disease Models
business
Articular
Peptide Hydrolases
Zdroj: Osteoarthritis and cartilage, vol 22, iss 10
ISSN: 1063-4584
DOI: 10.1016/j.joca.2014.07.011
Popis: Summary 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.
Databáze: OpenAIRE
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