This project is designed to establish novel treatments to decrease the risk of PTOA, and to investigate new diagnostic tools to identify patients at high risk of PTOA. The goal is to provide effective immediate preclinical information to support clinical application of these treatments and diagnostic tools. The treatments of interest are: 1) cytoprotective treatment that prevents immediate necrotic and acute apoptotic chondrocyte death at/near a site of acute cartilage injury, and 2) chondrocyte metabolic enhancement treatment developed to improve chondrocyte energy production, to restore anabolic function, and to suppress catabolic activities, by modulating the injury-related acute inflammatory response. These treatments will be piloted using a survival rabbit model. In this model, after controlled surgical insults that replicate major factors contributing to pathogenesis of human PTOA following joint injuries (i.e., acute joint injury and excessive cumulative mechanical stress to the injured cartilage), progressive cartilage loss predictably develops in the experimental joints (knees) in a relatively short period (8 weeks). Using this animal model of rapid-progression PTOA, work is proposed to test if the above treatments are capable of mitigating the early biologically mediated disease process of PTOA in vivo, and whether the treatments effectively decrease subsequent cartilage loss. The diagnostic tools of interest are: 1) MR imaging that visualizes/measures inflammatory anatomical changes and early intra-cartilage degenerative changes prior to cartilage loss, and 2) molecular biomarker analysis that measures whole-joint inflammation and whole-joint cartilage metabolic activity. The diagnostic power of these clinically applicable non- or minimally-invasive tools will be tested in a goat survival model of acute cartilage injury (created by means of precisely controlled blunt impaction insult). Work is proposed to test if these tools are capable of characterizing the severity of acute joint injury in vivo (particularly focusing on cartilage damage), and to test if subsequent progression of cartilage loss in these joints is reliably predictable using the early (<1 month) information provided by these diagnostic tools.

Public Health Relevance

This project will provide preclinical evidence that supports promise of a novel acute treatment strategy to effectively ameliorate the disease process of PTOA, and it will demonstrate the capability of the diagnostic methods to identify patients at high risk of PTOA. These advancements will accelerate translational research to improve treatment of joint injuries, to decrease the risk of PTOA.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center (P50)
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Special Emphasis Panel (ZAR1-KM)
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University of Iowa
Iowa City
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Townsend, Kevin C; Thomas-Aitken, Holly D; Rudert, M James et al. (2018) Discrete element analysis is a valid method for computing joint contact stress in the hip before and after acetabular fracture. J Biomech 67:9-17
Seol, Dongrim; Tochigi, Yuki; Bogner, Ashley M et al. (2018) Effects of knockout of the receptor for advanced glycation end-products on bone mineral density and synovitis in mice with intra-articular fractures. J Orthop Res 36:2439-2449
Thomas-Aitken, Holly D; Willey, Michael C; Goetz, Jessica E (2018) Joint contact stresses calculated for acetabular dysplasia patients using discrete element analysis are significantly influenced by the applied gait pattern. J Biomech 79:45-53
Coleman, Mitchell C; Goetz, Jessica E; Brouillette, Marc J et al. (2018) Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis. Sci Transl Med 10:
Ding, Lei; Buckwalter, Joseph A; Martin, James A (2017) DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone. Mediators Inflamm 2017:2642549
Segal, Neil A; Frick, Eric; Duryea, Jeffrey et al. (2017) Comparison of tibiofemoral joint space width measurements from standing CT and fixed flexion radiography. J Orthop Res 35:1388-1395
Segal, Neil A; Bergin, John; Kern, Andrew et al. (2017) Test-retest reliability of tibiofemoral joint space width measurements made using a low-dose standing CT scanner. Skeletal Radiol 46:217-222
Dibbern, Kevin; Kempton, Laurence B; Higgins, Thomas F et al. (2017) Fractures of the tibial plateau involve similar energies as the tibial pilon but greater articular surface involvement. J Orthop Res 35:618-624
Kapitanov, Georgi I; Ayati, Bruce P; Martin, James A (2017) Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis. PeerJ 5:e3468
Martin, James A; Anderson, Donald D; Goetz, Jessica E et al. (2017) Complementary models reveal cellular responses to contact stresses that contribute to post-traumatic osteoarthritis. J Orthop Res 35:515-523

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