Anterior cruciate ligament (ACL) injury is prevalent and often leads to instability, quadriceps muscle weakness and osteoarthritis. (OA) Many of those with chronic ACL deficiency have evidence of knee OA years after ACL rupture. Weakness and instability experienced by those who do not compensate well for ACL deficiency (non-copers) independently lead to compensation strategies that could precipitate or worsen knee OA. These poor compensation strategies do not uniformly resolve after surgical reconstruction and those who undergo reconstruction also have an increased risk of developing knee OA. The overall goal of this work is to determine whether effective rehabilitation programs to dynamically stabilize the knee reduce the adaptations that lead to osteoarthritis in a population at great risk for the development of knee OA. Eighty individuals with ACL rupture who are scheduled for surgery will be randomly assigned to a group that includes a form of neuromuscular training called perturbation training, or a standard group. They will be evaluated before and after surgery using motion analysis and radiography. In vivo measures of kinematics, kinetics, tibial translation and EMG based models of joint compression will be used for comparison. This randomized trial is designed to demonstrate that, after preoperative rehabilitation that includes perturbation training, movement patterns adopted by non-copers: 1) demonstrate improve joint stability and reduced muscle cocontraction, 2) persist after reconstruction and 3) result in better functional outcomes after reconstruction and 4) lead to the development of less knee pain and OA over time than standard preoperative treatment strategies. The information derived from this project will provide valuable insight into the management of the approximately 100,000 Americans who rupture their ACLs each year and undergo reconstructive surgery. More importantly, if the perturbation training program's ability to induce dynamic knee stability actually results in joint protection, its application to others at risk for the development knee OA may help reduce the incidence of this disabling clinical condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR048218-05S1
Application #
7219744
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Sharrock, William J
Project Start
2002-04-01
Project End
2008-03-31
Budget Start
2006-04-12
Budget End
2008-03-31
Support Year
5
Fiscal Year
2006
Total Cost
$17,658
Indirect Cost
Name
Yale University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Zhang, Ming-Zhu; Ferrigno, Olivier; Wang, Zhe et al. (2015) TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis. Cancer Cell 27:547-60
Addison, William N; Fu, Martin M; Yang, Helen X et al. (2014) Direct transcriptional repression of Zfp423 by Zfp521 mediates a bone morphogenic protein-dependent osteoblast versus adipocyte lineage commitment switch. Mol Cell Biol 34:3076-85
Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki et al. (2013) Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. J Exp Med 210:969-85
Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa et al. (2012) Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus. J Bone Miner Res 27:1649-58
Kang, Sona; Akerblad, Peter; Kiviranta, Riku et al. (2012) Regulation of early adipose commitment by Zfp521. PLoS Biol 10:e1001433
Hesse, Eric; Saito, Hiroaki; Kiviranta, Riku et al. (2010) Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. J Cell Biol 191:1271-83
Correa, Diego; Hesse, Eric; Seriwatanachai, Dutmanee et al. (2010) Zfp521 is a target gene and key effector of parathyroid hormone-related peptide signaling in growth plate chondrocytes. Dev Cell 19:533-46
Hesse, Eric; Kiviranta, Riku; Wu, Meilin et al. (2010) Zinc finger protein 521, a new player in bone formation. Ann N Y Acad Sci 1192:32-7
Rowe, Glenn C; Choi, Cheol Soo; Neff, Lynn et al. (2009) Increased energy expenditure and insulin sensitivity in the high bone mass DeltaFosB transgenic mice. Endocrinology 150:135-43
Wu, Meilin; Hesse, Eric; Morvan, Frederic et al. (2009) Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and promotes bone formation in vivo. Bone 44:528-36

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