In osteoarthritis the integrity of articular cartilage is damaged, compromising both the mechanical functioning and the self-repair capability of the tissue. The goal of this project is to elucidate the roles of collagen and proteoglycan in the biomechanical and homeostatic functions of normal and osteoarthritic cartilage.
The specific aims of this proposal are: to characterize the molecular packing of the collagen fibrils and the fixed charged density of proteoglycans in the articular cartilage of the knee as a function of topography and age, with the view of evaluating how the structures and properties of the macromolecules in articular cartilage depend on their mechanochemical history; to characterize the mechanisms of interaction between proteoglycans and collagen as a function of age and site in articular cartilages; and to elucidate the determinants of fibril swelling and compressibility of the collagen in articular cartilage as compared to those bone and soft tissues. The fibril orientation, and their relative alignment and compressibility throughout cartilages will be determined by X-ray diffraction techniques. The axial periodicity, the lateral distances between molecules in the fibrils, and other regularities in the molecular packing will also be characterized by x-ray diffraction. The space occupied by collagen fibrils as well as the state of the charged residues in the cartilage collagen fibrils will be measured by physical chemical methods. The charge density distribution and the mechanism of action of the endogenous force fields that are generated in cartilages by proteoglycans will be characterized using optical and physical chemical methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR037604-06A1
Application #
3158240
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1986-08-01
Project End
1996-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Yamauchi, M; Chandler, G S; Tanzawa, H et al. (1996) Cross-linking and the molecular packing of corneal collagen. Biochem Biophys Res Commun 219:311-5
Yamauchi, M; Katz, E P (1993) The post-translational chemistry and molecular packing of mineralizing tendon collagens. Connect Tissue Res 29:81-98
Katz, E P; David, C W (1992) Unique side-chain conformation encoding for chirality and azimuthal orientation in the molecular packing of skin collagen. J Mol Biol 228:963-9
Dziedzic-Goclawska, A; Toverud, S U; Kaminski, A et al. (1992) Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs. Bone Miner 19:127-43
Volpi, M; Katz, E P (1991) On the adaptive structures of the collagen fibrils of bone and cartilage. J Biomech 24 Suppl 1:67-77
Maroudas, A; Wachtel, E; Grushko, G et al. (1991) The effect of osmotic and mechanical pressures on water partitioning in articular cartilage. Biochim Biophys Acta 1073:285-94
Katz, E P; David, C W (1990) Energetics of intrachain salt-linkage formation in collagen. Biopolymers 29:791-8
Katz, E P; Wachtel, E; Yamauchi, M et al. (1989) The structure of mineralized collagen fibrils. Connect Tissue Res 21:149-54;discussion 155-8