There is a lack of a clear understanding of the contribution of specific matrix components to the mechanical properties of articular cartilage. The investigator has developed a cell line which will synthesize a mechanically testable cartilaginous matrix and have identified several variants of this line which synthesize an abnormal proportion of various matrix components, including chondroitin sulfate, aggrecan, and type IX collagen. The investigator proposes to use these mutant cell lines to examine how alterations in structures affect the assemble of the matrix and the mechanical properties of the resulting tissue.
Three specific aims are proposed. 1) Examine the contribution of the sulfate moiety on the proteoglycans to tissue formation and function with a mutant chondrocyte cell line which makes an undersulfated proteoglycan. 2) Examine the role of the chondroitin sulfate glycosaminoglycan component of proteoglycans to tissue formation and function by decreasing the amount of chondroitin sulfate on the proteoglycan with beta-xyloside inhibition. 3) Examine the effects of changing the relative proportions of selected matrix macromolecules on matrix assembly and mechanical properties. The matrices formed will be analyzed to determine proteoglycan synthesis, content and structure and aggregation, collagen content and type, morphology, immunolocalization, and mechanical properties.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014379-02
Application #
2457598
Study Section
Special Emphasis Panel (ZRG4-OBM-2 (01))
Program Officer
Finkelstein, David B
Project Start
1996-08-07
Project End
2000-07-31
Budget Start
1997-08-15
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Orthopedics
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202