Recent data suggest that there are multiple regulatory pathways by which chondrocytes sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation and post-translational modifications, and cell-mediated extracellular assembly and degradation of matrix. Correspondingly, there may be multiple pathways by which physical stimuli can alter not only the rate of matrix production, but the quality and functionality of newly synthesized proteoglycans, collagens, and other molecules. In this manner, specific mechanical loading regimes may either enhance or compromise the ultimate biomechanical function of cartilage. We propose to (1) Quantify the effects of static, dynamic, and injurious compression on the morphology of intracellular organelles within chondrocytes of cartilage explants; (2) Quantify the effects of static, dynamic, and injurious compression on changes in the intracellular localization and activity of chondroitin 6-0-sulfotransferase (C6ST) transfected into primary bovine chondrocytes that are seeded into alginate gel disks subjected to compression; (3) Determine the effects of graded levels of injurious strain and strain rate on cell viability; on mRNA levels for aggrecan, collagen types I, IIA, IIB, and selected matrix metalloproteinases; on changes in morphology of intracellular organelles; and on cell-level spatial profiles of matrix turnover, and (4) Quantify the biosynthetic response of human cartilages to static, dynamic and injurious compression, using tissue from the distal femur, tibial plateau, and talocrural joint surfaces, and identify biosynthetic and degradative responses at the tissue and cell levels as a function of tissue age, location, and position.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045779-04
Application #
6375188
Study Section
Special Emphasis Panel (ZAR1-TLB-B (O3))
Program Officer
Tyree, Bernadette
Project Start
1998-09-30
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
2001
Total Cost
$218,467
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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