Osteoarthritis (OA) is a debilitating and painful joint disease affecting an estimated 12% of the total United States population between 25-74 years of age. The incedence is even greater among obese individuals. The goal of this study is to understand how exercise training affects the pathogenesis of obesity-linked OA. We hypothesize that moderate exercise training mitigates and delays the onset of OA in diet-induced obese mice. To test this, we will study non-obese sedentary, obese sedentary, and obese exercise-trained mice. For each group we will determine: 1) voluntary cage activity levels, preferred speeds, and gait characteristics to better understand the factors affecting joint loading, 2) serum levels of pro-inflammatory cytokines (e.g. ILl, IL-17, and TNF-alpha), nitric oxide, and prostaglandins to understand the role of systemic inflammation in the pathogenesis of OA, and 3) compressive and tensile properties and histological grades of knee joint cartilage to quantify the parameters of cartilage degeneration that characterize OA. These studies will significantly improve our understanding of different mechanisms involved in the pathogenesis of OA and the efficacy of """"""""biomechanical"""""""" therapies such as weight-loss and exercise in decreasing disease progression. ? ?
| Griffin, Timothy M; Huebner, Janet L; Kraus, Virginia B et al. (2012) Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise. Arthritis Rheum 64:443-53 |
| Costello, Kerry E; Guilak, Farshid; Setton, Lori A et al. (2010) Locomotor activity and gait in aged mice deficient for type IX collagen. J Appl Physiol 109:211-8 |
| Griffin, Timothy M; Fermor, Beverley; Huebner, Janet L et al. (2010) Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Ther 12:R130 |
| Allen, Kyle D; Griffin, Timothy M; Rodriguiz, Ramona M et al. (2009) Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum 60:2684-93 |
| Griffin, Timothy M; Huebner, Janet L; Kraus, Virginia B et al. (2009) Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum 60:2935-44 |
| Griffin, Timothy M; Guilak, Farshid (2008) Why is obesity associated with osteoarthritis? Insights from mouse models of obesity. Biorheology 45:387-98 |
| Hanna, Jandy B; Schmitt, Daniel; Griffin, Timothy M (2008) The energetic cost of climbing in primates. Science 320:898 |
| Schmitt, Daniel; Cartmill, Matt; Griffin, Timothy M et al. (2006) Adaptive value of ambling gaits in primates and other mammals. J Exp Biol 209:2042-9 |
| Griffin, Timothy M; Guilak, Farshid (2005) The role of mechanical loading in the onset and progression of osteoarthritis. Exerc Sport Sci Rev 33:195-200 |
