Abstract
The properties of different connective tissues depend on the synthesis and assembly of macromolecular structures composed of collagen and other extracellular matrix components. Mechanisms modulating these events play important roles in the formation of a functional tissue. We have studied the role of collagen-binding extracellular matrix leucine-rich repeat glycoproteins/proteoglycans in the formation of collagen matrices.
A region in decorin with high affinity for collagen type I was identified. Using a mammalian cell expression system we produced recombinant chimeric proteoglycans consisting of decorin sequences fused with biglycan sequences. Biglycan is closely related to decorin but does not bind to collagen type I. The collagen-binding properties of the proteoglycans and the proteoglycan chimeras were investigated in collagen fibril formation/sedimentation assays. The chimeric proteoglycan consisting of biglycan, substituted with leucine-rich repeats 4-5 from decorin, bound collagen type I. This region represents 13% of the amino acid sequence of decorin and contains a major collagen binding site.
To study the function of fibromodulin in vivo, a mouse strain lacking the expression of this proteoglycan was generated by gene targeting. These mice phenotypically showed abnormal collagen fibrils in tendons, suggesting a role for fibromodulin in collagen fibrillogenesis. Moreover, these fibromodulin-null mice showed an increased lumican deposition in tendons. Using both recombinant fibromodulin and lumican in collagen fibril formation/sedimentation assays, we showed that fibromodulin and the closely related lumican share a binding region on collagen type I fibrils. The binding of fibromodulin to collagen occurs with higher affinity than the binding of lumican.
A region in decorin with high affinity for collagen type I was identified. Using a mammalian cell expression system we produced recombinant chimeric proteoglycans consisting of decorin sequences fused with biglycan sequences. Biglycan is closely related to decorin but does not bind to collagen type I. The collagen-binding properties of the proteoglycans and the proteoglycan chimeras were investigated in collagen fibril formation/sedimentation assays. The chimeric proteoglycan consisting of biglycan, substituted with leucine-rich repeats 4-5 from decorin, bound collagen type I. This region represents 13% of the amino acid sequence of decorin and contains a major collagen binding site.
To study the function of fibromodulin in vivo, a mouse strain lacking the expression of this proteoglycan was generated by gene targeting. These mice phenotypically showed abnormal collagen fibrils in tendons, suggesting a role for fibromodulin in collagen fibrillogenesis. Moreover, these fibromodulin-null mice showed an increased lumican deposition in tendons. Using both recombinant fibromodulin and lumican in collagen fibril formation/sedimentation assays, we showed that fibromodulin and the closely related lumican share a binding region on collagen type I fibrils. The binding of fibromodulin to collagen occurs with higher affinity than the binding of lumican.
| Original language | English |
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| Qualification | Doctor |
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| Award date | 1999 Nov 12 |
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| ISBN (Print) | 91-628-3787-7 |
| Publication status | Published - 1999 |
Bibliographical note
Defence detailsDate: 1999-11-12
Time: 10:15
Place: Kemicentrum, sal B, Lund
External reviewer(s)
Name: Hardingham, Timothy
Title: Professor
Affiliation: Manchester University, UK
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The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Cell and Matrix Biology (LUR000002)
Subject classification (UKÄ)
- Cell and Molecular Biology
Free keywords
- reumatologi
- muskelsystem
- Skelett
- decorin
- Collagen
- fibromodulin
- extracellular matrix
- lumican
- collagen fibrillogenesis
- Skeleton
- rheumatology locomotion
- muscle system
- Biochemistry
- Biokemi
- Metabolism