title: Changes in Structural-Mechanical Properties and Degradability of Collagen during Aging-associated Modifications.
abstract: During aging, changes occur in the collagen network that contribute to various pathological phenotypes in the skeletal, vascular, and pulmonary systems. The aim of this study was to investigate the consequences of age-related modifications on the mechanical stability and in vitro proteolytic degradation of type I collagen. Analyzing mouse tail and bovine bone collagen, we found that collagen at both fibril and fiber levels varies in rigidity and Young's modulus due to different physiological changes, which correlate with changes in cathepsin K (CatK)-mediated degradation. A decreased susceptibility to CatK-mediated hydrolysis of fibrillar collagen was observed following mineralization and advanced glycation end product-associated modification. However, aging of bone increased CatK-mediated osteoclastic resorption by ∼27%, and negligible resorption was observed when osteoclasts were cultured on mineral-deficient bone. We observed significant differences in the excavations generated by osteoclasts and C-terminal telopeptide release during bone resorption under distinct conditions. Our data indicate that modification of collagen compromises its biomechanical integrity and affects CatK-mediated degradation both in bone and tissue, thus contributing to our understanding of extracellular matrix aging.
authors.affiliation: From the Department of Oral Biological and Medical Sciences, Faculty of Dentistry, Center for Blood Research.
authors.forename: Preety
authors.initials: P
authors.lastname: Panwar
authors.affiliation: the Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamour
authors.affiliation: From the Department of Oral Biological and Medical Sciences, Faculty of Dentistry, Center for Blood Research.
authors.forename: Neil C W
authors.initials: NC
authors.lastname: Mackenzie
authors.affiliation: Department of Mechanical Engineering, and.
authors.forename: Heejae
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Mechanical Engineering, and.
authors.forename: Frank
authors.initials: F
authors.lastname: Ko
authors.affiliation: the Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Oral Biological and Medical Sciences, Faculty of Dentistry, Center for Blood Research, the Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia 6T 1Z3 and dbromme@dentistry.ubc.ca.
authors.forename: Dieter
authors.initials: D
authors.lastname: Brömme
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000378:metabolism*; D055119:Elastic Modulus; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D059748:Proteolysis
chemical_list: D003094:Collagen; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: aging; atomic force microscopy (AFM); cathepsin K; collagen; cysteine protease; electron microscopy (EM); osteoclast