Exercise and Dietary Interventions in a Rat Model of Metabolic Knee Osteoarthritis

Osteoarthritis is a debilitating chronic disease which has no cure or effective treatment. If no changes are made in prevention and treatment, osteoarthritis will continue to represent a significant economic burden to patients and society. The goal of this thesis was to determine the effects of moderate aerobic exercise and prebiotic fibre supplementation on the onset and progression of the metabolic knee osteoarthritis phenotype in rats exposed to a high-fat/highsucrose diet. This study was divided into three phases. Phase 1: we evaluated the effects of a 12- week aerobic exercise program of varying duration on healthy rat knee cartilage. We determined that moderate, high and extra-high duration treadmill exercise has no detrimental effects on knee joint health, function and integrity. Therefore, we concluded that treadmill exercise at any tested duration was a safe exercise for rats in terms of knee osteoarthritis-like damage, and therefore, could be used as a safe exercise intervention in a pre-clinical rat model of knee osteoarthritis. Phase 2: we evaluated the effects of moderate aerobic exercise, prebiotic fibre supplementation, and the combination of exercise and fibre over a 12-week intervention in rats exposed to a high-fat/highsucrose diet that has been shown to cause knee joint damage. Our findings indicated that prebiotic fibre and aerobic exercise prevented knee joint damage in this model. Phase 3: we evaluated if the damaging effects of the high-fat/high-sucrose diet could be delayed/reversed. We determined that neither prebiotic fibre supplementation nor aerobic exercise were able to stop the progression of existing knee osteoarthritis-like damage induced by a high-fat/high-sucrose diet. In summary, this thesis provides insight into two different approaches to prevent the development of metabolic osteoarthritis phenotype. However, the studies presented in this thesis were not able to show an effective way to stop the progression of the disease.

Year	Entry
2005	Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma H-L, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. March 31, 2005;434(7033):644-648.
2007	Furman BD, Strand J, Hembree WC, Ward BD, Guilak F, Olson SA. Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis. J Orthop Res. May 2007;25(5):578-592.
2007	Faul F, Erdfelder E, Lang A-G, Buchner A. GPower 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods*. May 2007;39(2):175-191.
1995	Haut RC, Ide TM, De Camp CE. Mechanical responses of the rabbit patello-femoral joint to blunt impact. J Biomech Eng. November 1995;117(4):402-408.
2005	De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. December 2005;37(6):810-818.
2001	Jakob M, Démarteau O, Schäfer D, Hintermann B, Dick W, Heberer M, Martin I. Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J Cell Biochem. May 1, 2001;81(2):368-377.
1971	Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips, II: correlation of morphology with biochemical and metabolic data. J Bone Joint Surg. April 1971;51A(3):523-537.
2012	Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. June 2012;64(6):1697-1707.
1981	Woo SL-Y, Gomez MA, Amiel D, Ritter MA, Gelberman RH, Akeson WH. The effects of exercise on the biomechanical and biochemical properties of swine digital flexor tendons. J Biomech Eng. February 1981;103(1):51-56.
2011	Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. June 18, 2011;377(9783):2115-2126.
2000	Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. January 21, 2000;100(2):197-207.
2013	Little CB, Hunter DJ. Post-traumatic osteoarthritis: from mouse models to clinical trials. Nat Rev Rheumatol. August 2013;9(8):485-497.
1961	Woessner JF Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. May 1961;93(2):440-447.
1999	Derwin KA, Soslowsky LJ. A quantitative investigation of structure-function relationships in a tendon fascicle model. J Biomech Eng. December 1999;121(6):598-604.
1991	Thompson RC Jr, Oegema TR Jr, Lewis JL, Wallace L. Osteoarthrotic changes after acute transarticular load: an animal model. J Bone Joint Surg. August 1991;73A(7):990-1001.
1998	Roos H, Laurén M, Adalberth T, Roos EM, Jonsson K, Lohmander LS. Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls. Arthritis Rheum. 1998;41(4):687-693.
1976	McDevitt CA, Muir H. Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog. J Bone Joint Surg. February 1976;58B(1):94-103.
2010	Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. November 2010;6(11):625-635.

Year

Entry

2005

Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma H-L, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. March 31, 2005;434(7033):644-648.

2007

Furman BD, Strand J, Hembree WC, Ward BD, Guilak F, Olson SA. Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis. J Orthop Res. May 2007;25(5):578-592.

2007

Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. May 2007;39(2):175-191.

1995

Haut RC, Ide TM, De Camp CE. Mechanical responses of the rabbit patello-femoral joint to blunt impact. J Biomech Eng. November 1995;117(4):402-408.

2005

De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. December 2005;37(6):810-818.