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Tendinosis and Tendon Regeneration: Roles of Apoptosis and Insulin-Like Growth Factor-I
February 2005
| Co-Principal Investigators: |
Vincent Duronio, Karim Khan ( University of British Columbia) |
| Co-investigators: | Alexander Scott ( University of British Columbia) |
For more information about this development grant project, please contact Dr. Vincent Duronio.
Issue
Tendon injuries are a common type of work-related musculoskeletal disorder. However, it is not currently well understood how tendon tissue becomes injured.
A potential explanation for the chronic nature of these injuries is apoptosis, a form of cell death that may reduce the regenerative capacity of tendons.
This project examined whether apoptosis is occurring in tendon injuries, and explored a potential new treatment involving insulin-like growth factor-1 (IGF-1), that may be able to target apoptosis in tendon injuries.
Key findings
- Apoptosis occurs in tendons undergoing mechanical loading in an
animal model.
- IGF-1 was able to prevent apoptosis in laboratory tests using a cell culture medium.
Objective
- To demonstrate tendon cell apoptosis using an animal model.
- To investigate whether IGF-1 prevents apoptosis and should be explored further as a potential treatment.
Method
An animal model (repetitive strain loading) was used to test for apoptosis in tendons. The researchers applied load to a rat tibialis anterior tendon specimen for 6 hours at 20% strain at a frequency of 1 Hz in a strain device. The right tibialis anterior tendons of three rats were loaded, and left tendons were prepared identically as non-loaded controls.
The role of IGF-1 was tested using tendon cells grown in a culture medium.
Results
Apoptosis occurred in the mechanically loaded tendons. Studies of tendon cells grown in a culture medium showed that apoptosis could be prevented from happening when IGF-I was included in the cell culture medium.
Conclusions
The results demonstrate that apoptosis occurs in tendons undergoing mechanical loading. The findings also suggest that IGF-1 warrants further investigation in the animal model, as a potential therapy.
Future directions
Further experiments can now be conducted to improve understanding the role of apoptosis in tendon injuries, and to develop a potential therapy for tendinopathy involving IGF-I.
Publications
Scott A, Khan KM, Duronio V. IGF-I activates PKB and prevents anoxic apoptosis in Achilles tendon cells. Journal of Orthopaedic Research. 2005 Sep;23(5):1219-25. Epub 2005 Apr 20.
Scott A, Khan KM, Heer J, Cook JL, Lian O, Duronio V. High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model. British Journal of Sports Medicine. 2005 May;39(5):e25.
Scott A, Duronio V. Understanding tendinopathies. British Journal of Sports Medicine. 2003 Jun;37(3):279.