title: Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.
abstract: Classic Ehlers-Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1+/-mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1+/-) with wild-type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1+/-tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild-type tendons, which recovered their pre-injury values by 6 weeks post injury. Additionally, the Col5a1+/-tendons demonstrated altered fibril morphology and diameter distributions compared to the wild-type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2707-2715, 2017.
authors.affiliation: University Laboratory Animal Resources, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Johnston
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Brianne K
authors.initials: BK
authors.lastname: Connizzo
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Snehal S
authors.initials: SS
authors.lastname: Shetye
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Robinson
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Julianne
authors.initials: J
authors.lastname: Huegel
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Rodriguez
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Adams
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: David E
authors.initials: DE
authors.lastname: Birk
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Louis J
authors.identifier: 0000-0001-7469-3039
authors.initials: LJ
authors.lastname: Soslowsky
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D024062:Collagen Type V / Q000502:physiology*; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000503:physiopathology*; D005260:Female; D057895:Haploinsufficiency; D008297:Male; D008810:Mice, Inbred C57BL; D013708:Tendon Injuries / Q000473:pathology / Q000503:physiopathology*; D013710:Tendons / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: C000623072:Col5a2 protein, mouse; D024062:Collagen Type V
keywords: Ehlers-Danlos syndrome; biomechanics; collagen V; injury; tendon