Fibromodulin distribution and association with collagen

Hedlund, Håkan; Mengarelli-Widholm, Silwa; Heinegård, Dick; Reinholt, Finn P.; Svensson, Olle

doi:10.1016/0945-053x(94)90186-4

Cited by 120 publications

(85 citation statements)

References 19 publications

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“…Examination of the distribution of fibromodulin on collagen fibrils has found it to be localized mainly in the gap region, axially within the D-period [27]. These workers also found that, in articular cartilage, levels of fibromodulin were higher in the interterritorial matrix than adjacent to cells and at the cartilage surface than at deeper levels.…”

Section: Introductionmentioning

confidence: 94%

Age-related changes in the structure of the keratan sulphate chains attached to fibromodulin isolated from articular cartilage

Lauder

Huckerby

Nieduszynski

et al. 1998

Biochemical Journal

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Bovine articular cartilage fibromodulin has been isolated from animals aged 3 months to 8 years, and the attached keratan sulphate (KS) chains digested with keratanase II. The oligosaccharides generated have been reduced, examined by high-pH anion-exchange chromatography and their structures identified by comparison with standards. It has been shown that in fibromodulin from young articular cartilage, the KS chains do not possess either non-reducing terminal (α2-6)-linked N-acetylneuraminic acid or fucose (α1-3)-linked to sulphated N-acetylglucosamine residues. However, an age-related increase has been observed in the abundance of both (α2-6)-linked N-acetylneuraminic acid and (α1-3)-linked fucose, neither of which is found in KS isolated from non-articular cartilage, irrespective of the age of the source. Interestingly, the KS chain length remains constant as a function of age, which possibly relates to a role in collagen fibril assembly. In addition, no significant age-related changes were identified in levels of galactose sulphation.

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Section: Introductionmentioning

confidence: 94%

Age-related changes in the structure of the keratan sulphate chains attached to fibromodulin isolated from articular cartilage

Lauder

Huckerby

Nieduszynski

et al. 1998

Biochemical Journal

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“…The uncalcified cartilage was stratified into three zones. The zones and the compartments around the cells were those defined previously (14,15).…”

Section: Figmentioning

confidence: 99%

“…Sampling from each of two blocks per animal (n ϭ 5) and measurements were performed as described elsewhere (14,15). Immunoreactivity was visualized with protein-A conjugated to 10-nm gold probes (Amersham Pharmacia Biotech, UK) in sections contrasted with uranyl acetate and lead citrate.…”

Section: Figmentioning

confidence: 99%

Association of the Aggrecan Keratan Sulfate-rich Region with Collagen in Bovine Articular Cartilage

Hedlund¹,

Hedbom²,

Heinegård³

et al. 1999

Journal of Biological Chemistry

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Aggrecan, the predominant large proteoglycan of cartilage, is a multidomain macromolecule with each domain contributing specific functional properties. One of the domains contains the majority of the keratan sulfate (KS) chain substituents and a protein segment with a proline-rich hexapeptide repeat sequence. The function of this domain is unknown but the primary structure suggests a potential for binding to collagen fibrils. We have examined binding of aggrecan fragments encompassing the KS-rich region in a solid-phase assay. A moderate affinity (apparent K d ‫؍‬ 1.1 M) for isolated collagen II, as well as collagen I, was demonstrated. Enzymatic digestion of the KS chains did not alter the capacity of the peptide to bind to collagen, whereas cleavage of the protein core abolished the interaction. The distribution of the aggrecan KS-rich region in bovine tarsometatarsal joint cartilage was investigated using immunoelectron microscopy. Immunoreactivity was relatively low in the superficial zone and higher in the intermediate and deep zones of the uncalcified cartilage. Within the pericellular and territorial matrix compartments the epitopes representing the aggrecan KSrich region were detected preferentially near or at collagen fibrils. Along the fibrils, epitope reactivity was non-randomly distributed, showing preference for the gap region within the D-period. Our data suggest that collagen fibrils interact with the KS-rich regions of several aggrecan monomers aligned within a proteoglycan aggregate. The fibril could therefore serve as a backbone in at least some of the aggrecan complexes.Articular cartilage matrix can be regarded as a fiber-reinforced composite material (1), where aggrecan complexes are entangled within a network of collagen fibrils. The aggrecan complexes, constituting about 90% of the proteoglycan content (2), endow the matrix with high osmotic pressure, compressive stiffness, and resilience, whereas collagen is essential for the tensile strength of the tissue (3). Different mechanical properties of the composite depend on these major constituents and how they are assembled and stabilized by intermolecular interactions. The capacity of cartilage to withstand mechanical stress depends upon its structural integrity and, hence, numerous interactions between the matrix components. Indeed, the molecules are so tightly associated that most of the tissue constituents require denaturing solvents or proteases for extraction. This has hampered studies of molecular function. To gain insight into the physiology of articular cartilage, it is necessary to identify and characterize interactions between the matrix constituents, particularly those involving the collagen.In the present study we focused on a domain of the aggrecan molecule containing the majority of the keratan sulfate (KS) 1 chain substituents and a protein segment with a hexapeptide repeat sequence (4). The second globular domain (G2) is localized adjacent to this KS-rich region, on the N-terminal side. The first globular domain (G1), which r...

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“…A differential distribution in articular cartilage has also been identified (Hedlund et al, 1994), fibromodulin being more abundant at the surface that at deeper levels. Nieduszynski et al (1990) have shown that, for 0-linked keratan sulphate chains from aggrecan, there is a distinction between chains from articular cartilage (KS-11-A), which contain a( 1-3)-linked fucose and a(2-6)-linked N-acetylneuraminic acid, and those from non-articular cartilage (KS-11-B) which contain neither of these features.…”

mentioning

confidence: 95%

“…Fibromodulin, along with the related small proteoglycan decorin, inhibits the formation of collagen fibrils in vitro (\'ogel et al, 1984;Hedbom and Heineglrd, 1989), and has been found to bind to collagens I and I1 (Hedbom and Heineglrd, 1989;Noyori and Jasin, 1994) being localised mainly in the gap region, axially within the D-period (Hedlund et al, 1994). A differential distribution in articular cartilage has also been identified (Hedlund et al, 1994), fibromodulin being more abundant at the surface that at deeper levels.…”

mentioning

confidence: 99%

The Structure of the Keratan Sulphate Chains Attached to Fibromodulin Isolated from Articular Cartilage

Lauder

Huckerby

Nieduszynski

1996

European Journal of Biochemistry

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Fibromodulin has been isolated from bovine and equine articular cartilage and the attached keratan sulphate chains subjected to digestion by keratanase 11. The oligosaccharides generated have been reduced and subsequently isolated by strong anion-exchange chromatography. Their structures have been determined by high-field 'H-NMR spectroscopy and high-pH anion-exchange chromatography.Both a(2-6)-and a(2-3)-linked N-acetylneuraminic acid have been found in the capping oligosaccharides, and, fucose which is a(l-3)-linked to N-acetylglucosamine has been found as a branch in both repeat region and capping oligosaccharides. These data demonstrate that there are fundamental differences between the structures present in the N-linked keratan sulphate chains attached to fibromodulin from articular cartilage and those from tracheal cartilage, which lack both a(2-6)-linked N-acetylneuraminic acid and a( 1 -3)-linked fucose.It has been confirmed that the keratan sulphate chains are short, being only eight or nine disaccharides in length. Very significant differences in the levels of galactose sulphation have been identified at the non-reducing end of the chain. The galactose residue adjacent to the non-reducing cap is sulphated in only 1-3% of chains, compared with a sulphation level of over 40% closer to the reducing end. This highlights the difference between the chain termini and the repeat region in terms of structure and points to the potential for functional importance.The repeat region and capping fragments of the N-linked keratan sulphates from bovine and equine articular cartilage fibromodulin have been found to have the following general structure : NeuAc-(a2-3/6)Ga1[6SO;] (PI-4) GlcNAc6SO; (pl-3) Gal [6SO,] (Pl-4) { [Fuc(al-3)],,GlcNAc6SO~ (pl-3)Gal-

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Fibromodulin distribution and association with collagen

Cited by 120 publications

References 19 publications

Age-related changes in the structure of the keratan sulphate chains attached to fibromodulin isolated from articular cartilage

Age-related changes in the structure of the keratan sulphate chains attached to fibromodulin isolated from articular cartilage

Association of the Aggrecan Keratan Sulfate-rich Region with Collagen in Bovine Articular Cartilage

The Structure of the Keratan Sulphate Chains Attached to Fibromodulin Isolated from Articular Cartilage

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