Degenerative joint disorders, such as arthritis, affect a substantial percentage of the US population and have a significant economic burden. The focused use of disease modifying drugs and cellular Strategies for tissue regeneration offer great potential to treat these disorders;however, the safety and efficacy of these treatment strategies must first be evaluated in pre-clinical models. The purposes of this proposal, and the career aims of the principal investigator, are to create and refine techniques to evaluate joint function and symptoms in pre-clinical, animal models of arthritis and to investigate the potential for disease-modifying therapeutics to modify functional and symptomatic sequelae associated with arthritis. This proposal begins with the mentored phase where interleukin 1p (IL-lp) overexpression in the knee joint will be used as a rat model of unilateral inflammatory arthritis. The functional and symptomatic sequelae of this arthritis will be evaluated using custom-designed gait and pain sensitivity tests. Moreover, two ILIp antagonists, interleukin 1 receptor antagonist (111 Ra) and soluble interleukin 1 receptor type II (slHRII), will be evaluated for their ability to modify functional and symptomatic sequelae associated with knee arthritis. The PI will then transition skills and knowledge gained during the mentored phase to the study of temporomandibular joint (TMJ) disorders and their functional and symptomatic sequelae. In the independent stage, techniques and methods to assess the sequelae of TMJ disorders will be developed for rodent models, including systems to evaluate orofacial sensitivity, bite force, dietary habits, and sleep patterns. The intra-articular ILip over-expression model will then be adapted to initiate TMJ arthritis, and the developed technologies will be applied and assessed for their ability to modify the associated functional and symptomal sequelae. This proposal addresses the developments of novel treatment and assessment strategies for knee arthritis and TMJ disorders, drawing significantly on the PI's experience in TMJ research and the mentor institution's expertise in osteoarthritis and drug delivery. Moreover, this research plan will assist the PI in transitioning to a faculty position and establish an independent research program evaluating therapeutic interventions for TMJ disorders and degeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Career Transition Award (K99)
Project #
5K99AR057426-02
Application #
7918054
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mao, Su-Yau
Project Start
2009-08-14
Project End
2011-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$82,373
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Kloefkorn, Heidi E; Pettengill, Travis R; Turner, Sara M F et al. (2017) Automated Gait Analysis Through Hues and Areas (AGATHA): A Method to Characterize the Spatiotemporal Pattern of Rat Gait. Ann Biomed Eng 45:711-725
Kloefkorn, Heidi E; Allen, Kyle D (2017) Quantitative histological grading methods to assess subchondral bone and synovium changes subsequent to medial meniscus transection in the rat. Connect Tissue Res 58:373-385
Yarmola, Elena G; Shah, Yash; Arnold, David P et al. (2016) Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis. Ann Biomed Eng 44:1159-69
Rohrs, Eric L; Kloefkorn, Heidi E; Lakes, Emily H et al. (2015) A novel operant-based behavioral assay of mechanical allodynia in the orofacial region of rats. J Neurosci Methods 248:1-6
Kloefkorn, Heidi E; Jacobs, Brittany Y; Loye, Ayomiposi M et al. (2015) Spatiotemporal gait compensations following medial collateral ligament and medial meniscus injury in the rat: correlating gait patterns to joint damage. Arthritis Res Ther 17:287
Jacobs, Brittany Y; Kloefkorn, Heidi E; Allen, Kyle D (2014) Gait analysis methods for rodent models of osteoarthritis. Curr Pain Headache Rep 18:456
Allen, Kyle D; Mata, Brian A; Gabr, Mostafa A et al. (2012) Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis. Arthritis Res Ther 14:R78
Hwang, Priscilla Y; Allen, Kyle D; Shamji, Mohammed F et al. (2012) Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy. Open Orthop J 6:383-91
Allen, Kyle D; Adams Jr, Samuel B; Mata, Brian A et al. (2011) Gait and behavior in an IL1?-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res 29:694-703
Allen, Kyle D; Shamji, Mohammed F; Mata, Brian A et al. (2011) Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism. Arthritis Res Ther 13:R137

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