Tenocyte responses to mechanical loading in vivo : A role for local insulin-like growth factor 1 signaling in early tendinosis in rats

Scott, Alexander, Cook, Jill, Hart, David A., Walker, David C., Duronio, Vincent and Khan, Karim M. 2007, Tenocyte responses to mechanical loading in vivo : A role for local insulin-like growth factor 1 signaling in early tendinosis in rats, Arthritis and rheumatism, vol. 56, no. 3, pp. 871-881.


Title Tenocyte responses to mechanical loading in vivo : A role for local insulin-like growth factor 1 signaling in early tendinosis in rats
Author(s) Scott, Alexander
Cook, Jill
Hart, David A.
Walker, David C.
Duronio, Vincent
Khan, Karim M.
Journal name Arthritis and rheumatism
Volume number 56
Issue number 3
Start page 871
End page 881
Publisher John Wiley & Sons, Inc.
Place of publication New York, N.Y.
Publication date 2007-03
ISSN 2326-5191
1529-0131
Summary Objective
To investigate tenocyte regulatory events during the development of overuse supraspinatus tendinosis in rats.

Methods
Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for 1 hour a day. Tendons were harvested at 4, 8, 12, and 16 weeks and processed for brightfield, polarized light, or transmission electron microscopy. The development of tendinosis was assessed semiquantitatively using a modified Bonar histopathologic scale. Apoptosis and proliferation were examined using antibodies against fragmented DNA or proliferating cell nuclear antigen, respectively. Insulin-like growth factor 1 (IGF-1) expression was determined by computer-assisted quantification of immunohistochemical reaction. Local IGF-1 signaling was probed using antibodies to phosphorylated insulin receptor substrate 1 (IRS-1) and ERK-1/2.

Results
Tendinosis was present after 12 weeks of downhill running and was characterized by tenocyte rounding and proliferation as well as by glycosaminoglycan accumulation and collagen fragmentation. The proliferation index was elevated in CD90+ tenocytes in association with tendinosis and correlated with increased local IGF-1 expression by tenocytes and phosphorylation of IRS-1 and ERK-1/2. Both apoptosis and cellular inflammation were absent at all time points.

Conclusion
In this animal model, early tendinosis was associated with local stimulation of tenocytes rather than with extrinsic inflammation or apoptosis. Our data suggest a role for IGF-1 in the load-induced tenocyte responses during the pathogenesis of overuse tendon disorders.
Notes Published Online: 27 Feb 2007
Language eng
Field of Research 111603 Systems Physiology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, American College of Rheumatology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007610

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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