Article (Scientific journals)
Collagen fibril disruption occurs early in primary guinea pig knee osteoarthritis.
Huebner, J. L.; Williams, J. M.; Deberg, Michelle et al.
2010In Osteoarthritis and Cartilage, 18 (3), p. 397-405
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Keywords :
Animals; Biological Markers/metabolism; Cartilage, Articular/metabolism; Collagen Type II/metabolism; Disease Models, Animal; Fibril-Associated Collagens/metabolism; Guinea Pigs; Immunohistochemistry; Knee Joint/pathology; Male; Osteoarthritis, Knee/pathology; Time Factors
Abstract :
[en] OBJECTIVE: A major barrier inhibiting the discovery of structural modifying agents for osteoarthritis (OA) is an incomplete understanding of early disease events. Herein, we investigated the time course of collagen II cleavage and fibril disruption in the well-validated Hartley guinea pig model of spontaneous OA of the knee. METHODS: Knee joints of 46 male Hartley guinea pigs were analyzed at 3 weeks, 2, 4, 7, 10, 12, and 18 months of age for histological severity of OA, cartilage collagen fibril disruption by semi-quantitative polarized light microscopy, and expression of type II collagen degradation biomarkers, 9A4 and Coll2-1, by immunohistochemistry. In addition, serum biomarkers specific for collagen II degradation, CTX-II, C2C, and Coll2-1 were quantified. RESULTS: Collagen fibril disruption and expression of the collagenase-generated cleavage neoepitope, 9A4, were observed as early as 2 months of age, despite the appearance of histological OA at 4 months of age. Only serum Coll2-1 increased coincident with the early disruption of the collagen fibril between 3 weeks and 7 months, in contrast to serum C2C, which did not change significantly or correlate with histological severity. Inversely, CTX-II declined dramatically from 3 weeks to 4 months and remaining low thereafter, coincident with growth plate turnover. CONCLUSIONS: Collagenase cleavage and disruption of the type II collagen network are early OA disease events in this model, preceding histological evidence of proteoglycan loss. The markedly different serum profiles of collagen II-related biomarkers during the early stages of disease development suggest compartmental segregation and temporal regulation of collagen degrading enzymes.
Disciplines :
Rheumatology
Author, co-author :
Huebner, J. L.
Williams, J. M.
Deberg, Michelle ;  Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Henrotin, Yves  ;  Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie
Kraus, V. B.
Language :
English
Title :
Collagen fibril disruption occurs early in primary guinea pig knee osteoarthritis.
Publication date :
2010
Journal title :
Osteoarthritis and Cartilage
ISSN :
1063-4584
eISSN :
1522-9653
Publisher :
W.B. Saunders, London, United Kingdom
Volume :
18
Issue :
3
Pages :
397-405
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Available on ORBi :
since 09 November 2010

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