Advanced

Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis

Ameye, L; Aria, D; Jepsen, K; Oldberg, Åke LU ; Xu, TS and Young, MF (2002) In FASEB Journal 16(7). p.673-680
Abstract
Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in biglycan and/or fibromodulin are structurally and mechanically altered resulting in unstable joints. As a result, the mice develop successively and progressively 1) gait impairment, 2) ectopic tendon ossification, and 3) severe premature osteoarthritis. Forced use of the joints increases ectopic ossification and osteoarthritis in the... (More)
Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in biglycan and/or fibromodulin are structurally and mechanically altered resulting in unstable joints. As a result, the mice develop successively and progressively 1) gait impairment, 2) ectopic tendon ossification, and 3) severe premature osteoarthritis. Forced use of the joints increases ectopic ossification and osteoarthritis in the double-deficient mice, further indicating that structurally weak tendons cause the phenotype. The study shows that mutations in SLRPs may predispose to osteoarthritis and offers a valuable and unique animal model for spontaneous osteoarthritis characterized by early onset and a rapid progression of the disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
proteoglycans, cartilage, leucine-rich, matrix, bone
in
FASEB Journal
volume
16
issue
7
pages
673 - 680
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • pmid:11978731
  • wos:000175973900021
  • scopus:0036235834
ISSN
1530-6860
DOI
10.1096/fj.01-0848com
language
English
LU publication?
yes
id
79482c53-45e2-4b15-8ef4-44d2d8f83154 (old id 336092)
date added to LUP
2007-08-02 10:48:16
date last changed
2017-12-10 04:24:45
@article{79482c53-45e2-4b15-8ef4-44d2d8f83154,
  abstract     = {Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in biglycan and/or fibromodulin are structurally and mechanically altered resulting in unstable joints. As a result, the mice develop successively and progressively 1) gait impairment, 2) ectopic tendon ossification, and 3) severe premature osteoarthritis. Forced use of the joints increases ectopic ossification and osteoarthritis in the double-deficient mice, further indicating that structurally weak tendons cause the phenotype. The study shows that mutations in SLRPs may predispose to osteoarthritis and offers a valuable and unique animal model for spontaneous osteoarthritis characterized by early onset and a rapid progression of the disease.},
  author       = {Ameye, L and Aria, D and Jepsen, K and Oldberg, Åke and Xu, TS and Young, MF},
  issn         = {1530-6860},
  keyword      = {proteoglycans,cartilage,leucine-rich,matrix,bone},
  language     = {eng},
  number       = {7},
  pages        = {673--680},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis},
  url          = {http://dx.doi.org/10.1096/fj.01-0848com},
  volume       = {16},
  year         = {2002},
}