Small animal models are attractive for studying the pathogenesis of osteoarthritis (OA) and for screening pharmacological agents and surgical strategies for treatment of OA. Articular cartilage exhibits dramatic changes in composition, metabolism and structure with OA which are associated with an impaired mechanical function as a weight-bearing material. Presently, there is no information on cartilage mechanics in small animal models (e.g., mice, rat, guinea pig) due to the limitations inherent in testing small tissue samples. In this project, we propose to quantify changes in cartilage mechanical properties in three small animal models of OA: (1) a guinea pig model of spontaneous OA; and two mouse models which exhibit early onset of degenerative joint disease (2) a mutant mouse model with a type XI collagen defect; and (3) a mutant mouse model with a type IX collagen defect. We hypothesize that disruption of the cartilage matrix, quantified as a decrease in the cartilage elastic modulus, is an early event in the progression of OA in these animal models. We propose to develop a new noncontacting method to determine the mechanical properties of cartilage in small animal joints.
Aim number 1 is to develop a chemical loading (swelling) experiment to determine material properties (elastic modulus and Poisson's ratio) of articular cartilage from the hip and knee joints of guinea pigs and mice. In preliminary tests of canine cartilage samples (1-4 mm thickness), material properties determined using this method were shown to be equivalent to those determined in a traditional tensile test, and to be capable of detecting changes in cartilage mechanics with joint degeneration. In this project, this method will be proportionally scaled for the testing of cartilage harvested from small animal models (50 -500 mum thickness) with use of bright-field and epifluorescence microscopy.
Aim number 2 is to quantify the temporal change in cartilage material properties in the guinea pig model of spontaneous OA.
Aim number 3 is to quantify differences in cartilage material properties in joints from wild-type and mutant mice with type XI and type IX collagen defects. The temporal changes in cartilage mechanics will also be studied in these models by quantifying material properties at early, middle and late stages of disease. This project will provide the first available data on degeneration-induced loss of cartilage function in the guinea pig and mouse joints. This data is expected to yield new insights into the pathogenesis of OA as well as the mechanical role of collagen types XI and IX in cartilage.
Showing the most recent 10 out of 14 publications
