The Effect of Proteoglycans on the Morphology of Collagen Fibrils Formed In Vitro

Vogel, Kathryn G.; Trotter, John A.

doi:10.1016/s0174-173x(87)80002-x

Cited by 316 publications

(223 citation statements)

References 26 publications

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“…Importance of DCN Structure on Inhibition-In agreement with previous studies, we found that the DCN core protein is critical for binding to collagen fibrils (43,44). Although dermatan sulfate and chondroitin sulfate bound to collagen beads, they did not, by themselves, influence collagen bead binding.…”

Section: ␣1(i)-(772-786)supporting

confidence: 91%

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Bhide

Laschinger

Arora

et al. 2005

Journal of Biological Chemistry

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Decorin is a small, leucine-rich proteoglycan that binds to collagen and regulates fibrillogenesis. We hypothesized that decorin binding to collagen inhibits phagocytosis of collagen fibrils. To determine the effects of decorin on collagen degradation, we analyzed phagocytosis of collagen and collagen/decorin-coated fluorescent beads by Rat-2 and gingival fibroblasts. Collagen beads bound to gingival cells by ␣2␤1 integrins. Binding and internalization of decorin/collagen-coated beads decreased dose-dependently with increasing decorin concentration (p < 0.001). Inhibition of binding was sustained over 5 h (p < 0.001) and was attributed to interactions between decorin and collagen and not to decorin-collagen receptor interactions. Both the nonglycosylated decorin core protein and the thermally denatured decorin significantly inhibited collagen bead binding (ϳ50 and 89%, respectively; p < 0.05). Mimetic peptides corresponding to leucine-rich repeats 1-3, encompassed by a collagen-binding ϳ11-kDa cyanogen bromide fragment of decorin and leucine-rich repeats 4 and 5, previously shown to bind to collagen, were tested for their ability to inhibit collagen bead binding. Although the synthetic peptide 3 alone exhibited saturable binding to collagen, neither peptides 3 nor 1 and 2 markedly inhibited phagocytosis. Leucine-rich repeat 3 bound to a triple helical peptide containing the ␣2 integrin-binding site of collagen. When collagen beads were co-incubated with peptides 3 and 4, inhibition of collagen phagocytosis (55%) was equivalent to intact native/ recombinant core protein. Thus a novel collagen binding domain in decorin acts cooperatively with leucinerich repeat 4 to mask the ␣2␤1 integrin-binding site on collagen, an important sequence for the phagocytosis of collagen fibrils.The intracellular phagocytic pathway in fibroblasts contributes to the physiological remodeling of collagen by lysosomal degradation of internalized collagen fibrils (1-4), but the mechanisms that regulate this pathway in vivo are poorly characterized. Previous morphological studies have shown that collagen fibrils are "decorated" by proteoglycans (5); consequently, decorin may affect the binding step of collagen phagocytosis (6).Decorin (DCN) 1 is a matrix proteoglycan that belongs to the small leucine-rich proteoglycan family (7). The mature form of DCN (ϳ100 kDa) consists of an ϳ45-kDa core protein, a single dermatan or chondroitin sulfate glycosaminoglycan chain, cysteine loops near the N and C terminus, and either two or three asparagine-bound oligosaccharides. The central part of the core protein consists of 10 leucine-rich repeat (LRR) sequences in tandem array (8). Rotary shadowing-electron microscopy and molecular modeling studies suggest that the DCN core protein is horseshoe-shaped (9, 10) and that the inner concavity accommodates and may provide a binding site for type I collagen (10). Indeed, DCN binds not only to type I but also to collagen types II, III, VI,. DCN binding to collagen molecules is thought to influence collagen fi...

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Section: ␣1(i)-(772-786)supporting

confidence: 91%

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Bhide

Laschinger

Arora

et al. 2005

Journal of Biological Chemistry

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“…Decorin has been found to be a potent regulator of collagen fibrillar-genesis, apparently by inhibiting the lateral association of collagen molecules by its prior binding (26)(27)(28). In an animal disease model where the decorin gene was disrupted, otherwise viable mice possessed fragile skin with reduced tensile strength, and abnormally large and irregularly shaped collagen fibrils were observed (29), similar traits to those seen in the human connective tissue disease Ehlers-Danlos syndrome.…”

Section: Implications For Molecular Interactions Within the Ecmmentioning

confidence: 90%

Microfibrillar structure of type I collagen in situ

Orgel

Irving

Miller

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

843

883

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The fibrous collagens are ubiquitous in animals and form the structural basis of all mammalian connective tissues, including those of the heart, vasculature, skin, cornea, bones, and tendons. However, in comparison with what is known of their production, turnover and physiological structure, very little is understood regarding the three-dimensional arrangement of collagen molecules in naturally occurring fibrils. This knowledge may provide insight into key biological processes such as fibrillo-genesis and tissue remodeling and into diseases such as heart disease and cancer. Here we present a crystallographic determination of the collagen type I supermolecular structure, where the molecular conformation of each collagen segment found within the naturally occurring crystallographic unit cell has been defined (P1, a Ϸ 40.0 Å, b Ϸ 27.0 Å, c Ϸ 678 Å, ␣ Ϸ 89.2°, ␤ Ϸ 94.6°, ␥ Ϸ 105.6°; reflections: 414, overlapping, 232, and nonoverlapping, 182; resolution, 5.16 Å axial and 11.1 Å equatorial). This structure shows that the molecular packing topology of the collagen molecule is such that packing neighbors are arranged to form a supertwisted (discontinuous) right-handed microfibril that interdigitates with neighboring microfibrils. This interdigitation establishes the crystallographic superlattice, which is formed of quasihexagonally packed collagen molecules. In addition, the molecular packing structure of collagen shown here provides information concerning the potential modes of action of two prominent molecules involved in human health and disease: decorin and the Matrix Metallo-Proteinase (MMP) collagenase.x-ray ͉ fiber ͉ crystallography ͉ fibril ͉ extracellular matrix A lthough the general features of the structure of type I collagen have been known for a long time, the specific packing arrangement of collagen molecules in situ has remained difficult to define, despite a great deal of effort by many investigators (1-16) (the general organization of type I collagen is summarized in Fig. 5, which is published as supporting information on the PNAS web site). Recently, we approached this difficult structural problem by employing conventional crystallographic techniques in x-ray fiber diffraction experiments (13,17,18), culminating in an initial electron density map (13, 19) that allowed a crude look at some aspects of the supermolecular arrangement of collagen molecules in situ. Unfortunately, the high degree of disorder observed in the gap region of the electron density map precluded the fitting of a molecular model to the electron density; the gap region was largely uninterpretable. Without the structure of the gap region, it was impossible to determine the overall molecular arrangement of collagen molecules in situ, and therefore its potential for improving our understanding of the structural, developmental, and pathological function of the collagen fibril at the molecular level remained unrealized. We have subsequently integrated additional (nonoverlapping) intensity data into the structural determination process (b...

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“…Various studies suggest that small proteoglycans that bind to collagen fibrils may have a role in regulation of collagen fibril length and diameter [34][35][36][37] and, consequently, of tensile integrity of connective tissues [38]. Removal of such components appears to enhance the association of collagen fibrils from tendon in vitro and in vivo [37,39] and enhance cartilage repair in vivo [40].…”

Section: Introductionmentioning

confidence: 99%

Articular cartilage tensile integrity: Modulation by matrix depletion is maturation-dependent

Asanbaeva

Tam

Schumacher

et al. 2008

Archives of Biochemistry and Biophysics

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Articular cartilage function depends on the molecular composition and structure of its extracellular matrix (ECM). The collagen network (CN) provides cartilage with tensile integrity, but must also remodel during growth. Such remodeling may depend on matrix molecules interacting with the CN to modulate the tensile behavior of cartilage. The objective of this study was to determine the effects of increasingly selective matrix depletion on tensile properties of immature and mature articular cartilage, and thereby establish a framework for identifying molecules involved in CN remodeling. Depletion of immature cartilage with guanidine, chondroitinase ABC, chondroitinase AC, and Streptomyces hyaluronidase markedly increased tensile integrity, while the integrity of mature cartilage remained unaltered after depletion with guanidine. The enhanced tensile integrity after matrix depletion suggests that certain ECM components of immature matrix serve to inhibit CN interactions and may act as modulators of physiological alterations of cartilage geometry and tensile properties during growth/maturation.

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The Effect of Proteoglycans on the Morphology of Collagen Fibrils Formed In Vitro

Cited by 316 publications

References 26 publications

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Microfibrillar structure of type I collagen in situ

Articular cartilage tensile integrity: Modulation by matrix depletion is maturation-dependent

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