Interplay Between Integrin Alpha 1 Beta 1 and Transforming Growth Factor Beta Receptor II in the Development of Spontaneous Osteoarthritis in the Mouse Knee

Integrin α1β1 is protective against the onset on spontaneous osteoarthritis (OA), however the mechanism by which integrin α1β1 exerts this effect is unknown. In this thesis we investigated the interplay between integrin α1β1 and TβRII in spontaneous OA in the knee utilizing the itga1-null mouse. We measured behavioural responses and the histological manifestations of spontaneous OA over a period of 16 months. We show that knee cartilage degeneration and collateral ligament calcifications gradually worsened, and that pain responses increased, with increasing age, and that TβRII drives early and severe knee OA in the medial compartment of itga1-null mice. In addition, we show that the frequency of collateral ligament calcifications is greater in the medial compartment and is increased in mice with a TβRII gene deletion in cartilage. As such, this thesis further supports integrin α1β1 as a novel therapeutic target for the treatment of OA via dampened TβRII signalling

Year	Entry
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2002	Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res. July 2002;20(4):842-848.
2015	Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45-54.
2008	Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.
2016	Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009.
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Year

Entry

2008

Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. November 2008;3(suppl 3):S131-S139.

2002

Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res. July 2002;20(4):842-848.

2015

Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45-54.

2008

Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.

2016

Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009.