Osteoarthritis (OA) is the most prevalent form of arthritis in the U.S., with knee OA being especially common and debilitating. One of the most clinically significant and modifiable risk factors for the development and progression of knee OA is obesity. Abnormal mechanical loading resulting from obesity is thought to be a cause for articular cartilage degeneration. In addition to alterations in the biomechanical environment of cartilage, changes in the composition of cartilage are hallmarks of disease progression. However, the precise mechanism of these influences is unclear. Establishing these relationships is important for understanding the role of obesity on cartilage composition and how these changes can subsequently affect the mechanical environment of cartilage. In this regard, quantitative MR imaging and 3-dimensional (3D) modeling techniques, such as the calculation of in vivo strain through changes in cartilage thickness, and T1-rho which has been correlated to proteoglycan content, could provide critical information regarding the effects of obesity on the mechanical and biochemical environment of cartilage. The overall goal of this proposal is to determine the effect of obesity on the biochemical and biomechanical environments of articular cartilage using MR imaging and 3D modeling techniques. We hypothesize that obesity causes a reduction in proteoglycan content within the cartilage (pre-OA), thereby decreasing the stiffness of cartilage and contributing to increased in vivo cartilage strains in response to mechanical loading. To test this hypothesis, we will use MR imaging and 3D modeling techniques to measure T1-rho relaxation times, which have been correlated to proteoglycan concentration, and to also measure in vivo cartilage strains.
In Specific Aim 1, we will measure the effect of obesity on the biochemical environment of the cartilage, specifically, proteoglycan concentration (via T1-rho weighted MR imaging) in obese and normal weight subjects.
In Specific Aim 2, we will measure tibiofemoral cartilage thickness distributions before and after a walking protocol in order to compare in vivo cartilage strains in the obese and normal BMI subject groups. These data will provide critical information on whether obesity influences OA progression through mechanical pathways alone, or through a combination of alterations in both the mechanical and biochemical environment of cartilage. Specifically, differences in both T1-rho relaxation times and cartilage strains between obese and normal subjects would suggest that obesity elevates OA risk through both biomechanical and biochemical pathways. Differences in cartilage strains with no change in T1- rho relaxation times between obese and normal weight subjects would suggest that mechanical factors play a dominant role in knee OA progression. Such results are expected to have an important positive impact, because understanding these relationships is a first step in developing appropriate strategies aimed at delaying progression of knee osteoarthritis.

Public Health Relevance

Knee osteoarthritis (OA) is a common and debilitating disease with many primary risk factors. One modifiable risk factor is obesity, which may contribute to changes in knee cartilage composition and subsequent abnormal loading of the joint. Using magnetic resonance (MR) imaging and 3-dimensional modeling of the knee joint, we will investigate the relationship of obesity to both in vivo cartilage composition and mechanical loading properties, which is a necessary first step in developing appropriate disease modifying strategies for knee OA.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Lester, Gayle E
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Duke University
Schools of Medicine
United States
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