Damage accumulation in tendons and tendon tears are a major source of musculoskeletal disability, afflicting the entire spectrum of society. Despite the importance of these problems, clinicians have little scientific basis for treatment recommendations because mechanisms whereby exercise may improve tendon homeostasis and resistance to injury, mechanisms responsible for the poor healing of fatigue damaged tendons, and the effect of activity on the healing of repaired diseased tendons are unknown. Previous studies have investigated the effects of exercise and laceration, but only in healthy tendon. We have developed and extensively characterized an in vivo model of fatigue damage accumulation in the rat patellar tendon, and now propose to study the response of fatigue damaged tendon to exercise and/or laceration. These studies, using this clinically relevant model of diseased tendons, will provide the foundation for novel and improved treatment strategies.

Public Health Relevance

The major goal of this project is to explore the effect of tendon overuse damage on the response of tenocytes to exercise and laceration. Successful completion of the proposed studies will provide the foundation for novel and improved treatment strategies for tendon injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR052743-09
Application #
8723739
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2005-09-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Orthopedics
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Fung, Ashley K; Paredes, J J; Andarawis-Puri, Nelly (2018) Novel image analysis methods for quantification of in situ 3-D tendon cell and matrix strain. J Biomech 67:184-189
Paredes, Juan; Shiovitz, David A; Andarawis-Puri, Nelly (2018) Uncorrelated healing response of tendon and ear injuries in MRL highlight a role for the local tendon environment in driving scarless healing. Connect Tissue Res 59:472-482
Bell, Rebecca; Gendron, N Remi; Anderson, Matthew et al. (2018) A potential new role for myofibroblasts in remodeling of sub-rupture fatigue tendon injuries by exercise. Sci Rep 8:8933
Titan, Ashley; Andarawis-Puri, Nelly (2016) Tendinopathy: Investigating the Intersection of Clinical and Animal Research to Identify Progress and Hurdles in the Field. JBJS Rev 4:
Paredes, J J; Andarawis-Puri, Nelly (2016) Therapeutics for tendon regeneration: a multidisciplinary review of tendon research for improved healing. Ann N Y Acad Sci 1383:125-138
Ratcliffe, Anthony; Butler, David L; Dyment, Nathaniel A et al. (2015) Scaffolds for tendon and ligament repair and regeneration. Ann Biomed Eng 43:819-31
Bell, R; Boniello, M R; Gendron, N R et al. (2015) Delayed exercise promotes remodeling in sub-rupture fatigue damaged tendons. J Orthop Res 33:919-25
Andarawis-Puri, Nelly; Philip, Anaya; Laudier, Damien et al. (2014) Temporal effect of in vivo tendon fatigue loading on the apoptotic response explained in the context of number of fatigue loading cycles and initial damage parameters. J Orthop Res 32:1097-103
Sereysky, Jedd B; Flatow, Evan L; Andarawis-Puri, Nelly (2013) Musculoskeletal regeneration and its implications for the treatment of tendinopathy. Int J Exp Pathol 94:293-303
Hamamura, Kazunori; Zhang, Ping; Zhao, Liming et al. (2013) Knee loading reduces MMP13 activity in the mouse cartilage. BMC Musculoskelet Disord 14:312

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