Dataset Information

Animal models of osteoarthritis: classification, update, and measurement of outcomes.

ABSTRACT: Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals.

SUBMITTER: Kuyinu EL

PROVIDER: S-EPMC4738796 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Animal models of osteoarthritis: classification, update, and measurement of outcomes.

Kuyinu Emmanuel L EL Narayanan Ganesh G Nair Lakshmi S LS Laurencin Cato T CT

Journal of orthopaedic surgery and research 20160202

Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under ...[more]

PMID: 26837951

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Project description:BACKGROUND:MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). METHODS:Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n?=?7/group) for 7 weeks. The four treatment groups were: (1) sham?+?vehicle; (2) ACLT?+?vehicle; (3) ACLT?+?MIV-711, 30 µmol/kg and (4) ACLT?+?MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n?=?15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. RESULTS:In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p?<?0.001) and CTX-II levels by up to 74% (p?<?0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p?<?0.001) and 80% (p?<?0.001), respectively. Synovial CTX-II levels were reduced by 55-57% (p?<?0.001) compared to baseline. MIV-711-treated animals had 25-37% lower macroscopic scores in the femur condyles and 13-33% lower macroscopic scores in the tibial plateaus. CONCLUSIONS:MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

Dataset Information

Animal models of osteoarthritis: classification, update, and measurement of outcomes.

Publications

Animal models of osteoarthritis: classification, update, and measurement of outcomes.

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