The objective of this project is to elucidate the pathophysiological mechanisms for tendinitis using a novel in vitro model and an animal model. The central working hypothesis in this project is that tendon fibroblasts are responsible for the development of tendinitis by producing PGE2, which is upregulated by increased expression levels of PLA2, COX-1 and COX-2, and that high levels of PGE2 cause dysfunction of the tendon fibroblasts, thus resulting in pathophysiological changes in tendons.
The specific aims of this project are: 1) to investigate the role of PLA2 and COX expression in the production of PGE2 by human tendon fibroblasts under repetitive mechanical stretching using a novel in vitro model; 2) to investigate the role of stretching-induced PGE2 in inflammatory gene expression, proliferation and collagen synthesis of the human tendon fibroblasts using a novel in vitro model; and 3) to determine the effect of repeated exposure of the patellar tendon to PGE2 on its biological, biochemical, and biomechanical properties in a rabbit model. To accomplish these aims, a multidisciplinary approach based on mechano-biology, molecular biology and biomechanics will be used.When completed, this project will provide insights into the pathophysiological mechanisms for tendinitis at the cellular and molecular levels. It will also provide clinically valuable data about the effect of repetitive inflammation due to PGE2 on the tendon structure and function, which will help develop strategies to prevent and treat tendinitis effectively. The findings from this study will also be useful in helping design experiments to study other repetitive motion disorders (e.g., carpal tunnel syndrome).

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR049921-01S1
Application #
6691648
Study Section
Special Emphasis Panel (ZOH1)
Program Officer
Panagis, James S
Project Start
2002-09-04
Project End
2006-08-31
Budget Start
2002-09-04
Budget End
2003-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$44,265
Indirect Cost
Name
University of Pittsburgh
Department
Orthopedics
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zhang, Jianying; Yuan, Ting; Wang, James H-C (2016) Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats. Oncotarget 7:8498-512
Wang, James H-C; Zhao, Guangyi; Li, Bin (2016) The Study of Cell Motility by Cell Traction Force Microscopy (CTFM). Methods Mol Biol 1365:301-13
Wang, James H-C; Nirmala, Xavier (2016) Application of Tendon Stem/Progenitor Cells and Platelet-Rich Plasma to Treat Tendon Injuries. Oper Tech Orthop 26:68-72
Zhang, Jianying; Wang, James H-C (2014) PRP treatment effects on degenerative tendinopathy - an in vitro model study. Muscles Ligaments Tendons J 4:10-7
Zhang, Jianying; Pan, Tiffany; Wang, James H-C (2014) Cryotherapy suppresses tendon inflammation in an animal model. J Orthop Translat 2:75-81
Zhang, Jianying; Wang, James H-C (2014) Prostaglandin E2 (PGE2) exerts biphasic effects on human tendon stem cells. PLoS One 9:e87706
Zhang, Jianying; Wang, James H-C (2013) The effects of mechanical loading on tendons--an in vivo and in vitro model study. PLoS One 8:e71740
Jiang, Dapeng; Wang, James H-C (2013) Tendinopathy and its treatment with platelet-rich plasma (PRP). Histol Histopathol 28:1537-46
Satish, Latha; O'Gorman, David B; Johnson, Sandra et al. (2013) Increased CCT-eta expression is a marker of latent and active disease and a modulator of fibroblast contractility in Dupuytren's contracture. Cell Stress Chaperones 18:397-404
Zhang, Jianying; Middleton, Kellie K; Fu, Freddie H et al. (2013) HGF mediates the anti-inflammatory effects of PRP on injured tendons. PLoS One 8:e67303

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