title: Cycle-dependent matrix remodeling gene expression response in fatigue-loaded rat patellar tendons.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hui B
authors.initials: HB
authors.lastname: Sun
authors.forename: Nelly
authors.initials: N
authors.lastname: Andarawis-Puri
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Li
authors.forename: David T
authors.initials: DT
authors.lastname: Fung
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Wang
authors.forename: Jelena
authors.initials: J
authors.lastname: Basta-Pljakic
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Leong
authors.forename: Jedd B
authors.initials: JB
authors.lastname: Sereysky
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ros
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Klug
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braman
authors.forename: Mitch B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Jepsen
authors.forename: Evan L
authors.initials: EL
authors.lastname: Flatow
mesh_terms: 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
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases