Tendon injuries affect millions of Americans in both occupational and athletic settings and cost billions of healthcare dollars every year. While mechanical loading is considered as a major causative factor responsible for tendon injuries, the molecular mechanisms that initiate translation of mechanical loading into tendon injuries remain unknown. In this study, we offer an innovative hypothesis that HMGB1, a well-established inflammation-related nuclear binding protein in major tissues and organs, is responsible for the onset of the tendon inflammatory cascade due to excessive mechanical loading placed on tendons. Specifically, we propose two aims in this study: 1) to determine the effects of various mechanical loading conditions on tendon cells using a novel in vitro model system; and 2) to determine the effects of mechanical over-loading conditions on mouse tendons in vivo using a well-established mouse treadmill running model. Cellular and molecular analyses will be performed to define the HMGB1 signaling cascade. This study represents the first efforts to determine the role of HMGB1 in the onset of tendon injuries. The successful completion of this study will reveal the early signaling mechanism that is responsible for the development of full blown tendinopathy often seen down-the-road in tendinopathic patients. This research endeavor will lead to new prevention and treatment strategies such as targeting HMGB1 by blocking its action that will be more effective than current tendinopathy treatment options, which are largely palliative.

Public Health Relevance

Tendon injuries are prevalent in both occupational and athletic settings, but current treatments of tendon injuries are largely palliative. A novel study is proposed to elucidate the molecular signaling mechanism that may be the first trigger responsible for the onset of tendon injury (tendon inflammation and/or degeneration) due to excessive mechanical loading placed on tendons. The findings of this study will help develop new protocols to prevent and treat tendon injuries more effectively in clinics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR070340-01
Application #
9165326
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Wang, Fei
Project Start
2016-07-20
Project End
2018-04-30
Budget Start
2016-07-20
Budget End
2017-04-30
Support Year
1
Fiscal Year
2016
Total Cost
$203,280
Indirect Cost
$71,280
Name
University of Pittsburgh
Department
Orthopedics
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Thampatty, Bhavani P; Wang, James H-C (2018) Mechanobiology of young and aging tendons: In vivo studies with treadmill running. J Orthop Res 36:557-565