title: ADAMTS5 is required for biomechanically-stimulated healing of murine tendinopathy.
abstract: A recently developed murine model of tendinopathy, induced by TGF-β1 injection, has been used to examine the reparative capacity of tendinopathic Achilles in Adamts5(-/-) mice. After TGF-β1 injection and 2 weeks of treadmill exercise, the Achilles from Adamts5(-/-) mice exhibited a reduction in maximum tensile stress of approximately 60%. However, in contrast to wild type mice previously characterized by this model, Adamts5(-/-) mice subjected to further treadmill exercise were unable to reverse this biomechanical deficit. This nonreparative phenotype was accompanied by a major deficiency, relative to wild-type, in expression of Col1a1 and Col3a1 and an abnormally elevated expression of a wide range of integrins. In addition, the tendinopathic Adamts5(-/-) mice showed a persistent accumulation of chondrogenic cells in the tendon body and an aggrecan-rich fibrocartilaginous matrix within disorganized collagen fiber bundles. Moreover, consistent with the compromised biomechanical properties of the Achilles in the Adamts5(-/-) mice, in vivo gait analysis revealed a strong trend (p = 0.07) towards increased swing time of the injected limb in Adamts5(-/-) relative to wild-type mice. These findings demonstrate that a deficiency in ADAMTS5 promotes a chondrogenic response to TGF-β1 injection that is not reversed by treadmill exercise. Hence, repair of biomechanically compromised tendons exhibiting midsubstance chondroid accumulation requires ADAMTS5.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois 60612, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bell
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Shewman
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Galante
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cole
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Bach
authors.forename: Karen L
authors.initials: KL
authors.lastname: Troy
authors.forename: Katalin
authors.initials: K
authors.lastname: Mikecz
authors.forename: John D
authors.initials: JD
authors.lastname: Sandy
authors.forename: Anna H
authors.initials: AH
authors.lastname: Plaas
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000071116:ADAMTS5 Protein; D000125:Achilles Tendon / Q000378:metabolism / Q000503:physiopathology*; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal / Q000502:physiology; D052256:Tendinopathy / Q000503:physiopathology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D053674:Aggrecans; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D016023:Integrins; D053773:Transforming Growth Factor beta1; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse
keywords: ADAMTS5; aggrecan; biomechanics; gait; gene expression; tendinopathy