The TMJ is a synovial joint subject to destruction from inflammatory diseases such as arthritis. The arthritic diseases involve cytokines and are associated with cartilage matrix degeneration. The exact mechanism for this degeneration is unknown but has been shown to involve the effector molecule nitric oxide. Nitric oxide has been shown to be markedly increased in chondrocytes in response to cytokine stimulation and this increase leads to inhibition of chondrocytes matrix biosynthesis. Continuous passive motion therapies yield beneficial effects on arthritic and inflamed synovial joints and are likely to involve mechanical activation using the Flexcell system markedly decreases production of nitric oxide in chondrocytes. Preliminary data indicate that mechanical activation using the Flexcell system markedly decreases production of nitric oxide in chondrocytes stimulated by inflammatory mediators. The applicant hypothesizes that this inhibition is due to a decrease in inducible nitric oxide synthases. This inhibition will led to improved matrix synthesis by chondrocytes. He proposes to determine if the inhibition of nitric oxide production in chondrocytes is a result of a decrease in inducible nitric oxide synthases and if matrix production is improved as a result of the inhibition of nitric oxide production. The project seeks to elucidate one mechanism by which the mechanical activity of continuous passive motion promotes healing of inflamed synovial joints.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15DE012976-01
Application #
2775331
Study Section
Special Emphasis Panel (ZRG4-GRM (03))
Project Start
1998-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Dentistry
Type
Schools of Dentistry
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Gassner, R; Buckley, M J; Georgescu, H et al. (1999) Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase. J Immunol 163:2187-92