Correlation between ?CT imaging- histology and functional capacity of the osteoarthritic knee in the rat model of osteoarthritis

Authors
Bagi CM, Zakur DE, Berryman E, Andresen CJ, Wilkie D

Lab
Pfizer Global Research & Development, Global Science & Technology, USA.

Journal
J Transl Med.

Abstract
BACKGROUND:
To acquire the most meaningful understanding of human arthritis, it is essential to select the disease model and methodology translatable to human conditions. The primary objective of this study was to evaluate a number of analytic techniques and biomarkers for their ability to accurately gauge bone and cartilage morphology and metabolism in the medial meniscal tear (MMT) model of osteoarthritis (OA).

METHODS:
MMT surgery was performed in rats to induce OA. A dynamic weight bearing system (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs in rats. At the end of a 10-week study cartilage pathology was evaluated by micro computed tomography (?CT), contrast enhanced ?CT (EPIC ?CT) imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization.

RESULTS:
The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by elevated CTX-II in serum, EPIC ?CT and histology. Bone analysis by ?CT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation.

CONCLUSIONS:
The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels. Results from this study suggest that use of histology, ?CT and EPIC ?CT, and functional DWB tests provide powerful combination to fully assess the key aspects of OA and enhance data interpretation.

BIOSEB Instruments Used:
Dynamic Weight Bearing 2.0 (BIO-DWB-DUAL)