title: Murine tendon function is adversely affected by aggrecan accumulation due to the knockout of ADAMTS5.
abstract: The present study examined the effect of ADAMTS5 (TS5) knockout on the properties of murine flexor digitorum longus (FDL) and Achilles tendons. FDL and Achilles tendons were analyzed using biomechanical testing, histology, and immunohistochemistry; further characterization of FDL tendons was conducted using transmission electron microscopy (collagen fibril ultrastructure), SDS-PAGE (collagen content and type), fluorescence-assisted carbohydrate electrophoresis for chondroitin sulfate and hyaluronan, and Western blotting for aggrecan, versican, and decorin abundance and distribution. FDL tendons of TS5(-/-) mice showed a 33% larger cross-sectional area, increased collagen fibril area fraction, and decreased material properties relative to those of wild type mice. In TS5(-/-) mice, aggrecan accumulated in the pericellular matrix of tendon fibroblasts. In Achilles tendons, cross-sectional area, stress relaxation, and structural properties were similar in TS5(-/-) and wild type mice; however, the TS5(-/-) tendons exhibited a higher tensile modulus and a weakened enthesis. These results demonstrate that TS5 deficiency disturbs normal tendon collagen organization and alters biomechanical properties. Hence, the role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function.
authors.affiliation: Departments of Orthopedic Surgery, Rheumatology/Internal Medicine, and Biochemistry, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois 60612, USA. vincent_wang@rush.edu
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Wang
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Bell
authors.forename: Ruchir
authors.initials: R
authors.lastname: Thakore
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Galante
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: John D
authors.initials: JD
authors.lastname: Sandy
authors.forename: Anna
authors.initials: A
authors.lastname: Plaas
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000125:Achilles Tendon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D053674:Aggrecans / Q000378:metabolism*; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D005260:Female; D024021:Fibril-Associated Collagens / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009929:Organ Size; D011509:Proteoglycans / Q000378:metabolism
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D024021:Fibril-Associated Collagens; D011509:Proteoglycans; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse