The goal of this investigation is to develop an animal model to study the role of abnormal mechanical loads in articular cartilage degeneration, particularly that analogous to osteoarthritis (OA) of the knee. The proposed model consists of a mechanical varus loading device (VLD) that is fixed to the hind limb of a New Zealand White rabbit. The VLD applies a varus moment of known magnitude to the knee while allowing normal joint function. This causes a quantifiable increase in tibio-femoral contact load, AP, in the medial joint compartment. The advances made with this new approach are that these load alterations can be modified or removed at any time, and that iatrogenic trauma is minimized because no intra-articular surgery is needed. At this stage, this work is considered exploratory because, while there exists an apparent corollary from clinical experience that aberrant mechanical overload contributes to loss of cartilage integrity, the exact empirical nature of the requisite overload is not known. Before proceeding with animal studies that are necessary to understand interventions that will either exacerbate or retard degenerative processes, we need to be confident that a particular chronic mechanical burden reliably initiates cartilage degeneration processes which are not self-mitigating. The study will test the primary hypothesis: the level of cartilage degeneration (as quantified by histological scoring) is dependent on the magnitude and duration of varus load applied to the knee. Additional measures of cartilage material properties and cartilage metabolism (as quantified by assays of CPU, C2C, and CS-846) will be explored for their dependence on the magnitude and duration of varus load applied to the knee. Currently, there is no model available to study the onset and early progression of OA produced by chronic abnormal loading such as occurs with joint malalignment. Our work will lead to a new model that will have the capability to study the early changes that occur in the degenerative process with a direct link to humans. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR052815-01A1
Application #
7093710
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2006-05-01
Project End
2008-02-28
Budget Start
2006-05-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$200,640
Indirect Cost
Name
University of Vermont & St Agric College
Department
Orthopedics
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Roemhildt, M L; Gardner-Morse, M G; Morgan, C F et al. (2014) Calcium phosphate particulates increase friction in the rat knee joint. Osteoarthritis Cartilage 22:706-9
Gardner-Morse, Mack; Badger, Gary; Beynnon, Bruce et al. (2013) Changes in in vitro compressive contact stress in the rat tibiofemoral joint with varus loading. J Biomech 46:1216-20
Roemhildt, M L; Beynnon, B D; Gauthier, A E et al. (2013) Chronic in vivo load alteration induces degenerative changes in the rat tibiofemoral joint. Osteoarthritis Cartilage 21:346-57
Roemhildt, Maria L; Beynnon, Bruce D; Gardner-Morse, Mack et al. (2012) Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits. J Orthop Res 30:1413-22
Roemhildt, M L; Beynnon, B D; Gardner-Morse, M et al. (2012) Tissue modification of the lateral compartment of the tibio-femoral joint following in vivo varus loading in the rat. J Biomech Eng 134:104501
Roemhildt, M L; Beynnon, B D; Gardner-Morse, M (2012) Mineralization of articular cartilage in the Sprague-Dawley rat: characterization and mechanical analysis. Osteoarthritis Cartilage 20:796-800
Gardner-Morse, Mack G; Tacy, Nelson J; Beynnon, Bruce D et al. (2010) In situ microindentation for determining local subchondral bone compressive modulus. J Biomech Eng 132:094502
Roemhildt, M L; Gardner-Morse, M; Rowell, C et al. (2010) Gait alterations in rats following attachment of a device and application of altered knee loading. J Biomech 43:3227-31
Roemhildt, Maria L; Coughlin, Kathryn M; Peura, Glenn D et al. (2010) Effects of increased chronic loading on articular cartilage material properties in the lapine tibio-femoral joint. J Biomech 43:2301-8