Cycle-dependent matrix remodeling gene expression response in fatigue-loaded rat patellar tendons.
Expression profiling of selected matrix remodeling genes was conducted to evaluate differences in molecular response to low-cycle (100) and high-cycle (7,200) sub-failure-fatigue loading of patellar tendons. Using our previously developed in vivo patellar tendon model, tendons were loaded for 100 or 7,200 cycles and expression of selected metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and collagens were quantified by real-time RT-PCR at 1- and 7-day post-loading. Expression profiles were also obtained from lacerated tendons as an acute injury model. The high-cycle group showed upregulation of TIMP-1, -2, Col3a1, and Col5a1, and downregulation TIMP-4 at both time points, upregulation of MMP-2 at 7-day post-loading and downregulation of MMP-13 and -14 at 1-day post-loading, suggesting overall repair/remodeling. In contrast, the low-cycle loaded group showed upregulation of MMP-2, -3, -13, and Col12a1 at both time points, upregulation of TIMP-1, -2, -3, Col3a1, and integrin β1 and downregulation of integrin α11 at 1-day post-loading and upregulation of Col1a1 at 7-day post-loading, consistent with a hypertrophic (adaptive) pattern. Lacerated tendons showed a typical acute wound response with upregulation of all examined remodeling genes. Differences found in tendon response to high- and low-cycle loading are suggestive of the underlying mechanisms associated with a healthy or damaging response.
Sun
Hui B
HB
Leni and Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1188, New York, New York 10029, USA.
Andarawis-Puri
Nelly
N
Li
Yonghui
Y
Fung
David T
DT
Lee
Jonathan Y
JY
Wang
Vincent M
VM
Basta-Pljakic
Jelena
J
Leong
Daniel J
DJ
Sereysky
Jedd B
JB
Ros
Stephen J
SJ
Klug
Raymond A
RA
Braman
Jonathan
J
Schaffler
Mitch B
MB
Jepsen
Karl J
KJ
Flatow
Evan L
EL
D000818:Animals; D001857:Bone Matrix / Q000378:metabolism / Q000503:physiopathology*; D016723:Bone Remodeling / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005221:Fatigue / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D023421:Models, Animal; D017847:Patellar Ligament / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology
D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases