Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone.

Li, S W; Prockop, Darwin J.; Helminen, Heikki J.; Fässler, Reinhard; Lapveteläinen, Tuomo; Király, Kari; Peltarri, A; Arokoski, Jari; Vaquette, Cédryck; Arita, Machiko

doi:10.1101/gad.9.22.2821

Cited by 224 publications

(152 citation statements)

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“…Another pertinent case is the collagen II-deficient mouse with inactivated Col2a1 alleles (53,54). Cartilages of these animals not only lack collagen II but also normal collagen XI, because that protein contains ␣3(XI) chains, i.e.…”

Section: Discussionmentioning

confidence: 99%

Macromolecular Specificity of Collagen Fibrillogenesis

Hansen

Brückner

2003

Journal of Biological Chemistry

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Suprastructures of the extracellular matrix, such as banded collagen fibrils, microfibrils, filaments, or networks, are composites comprising more than one type of macromolecule. The suprastructural diversity reflects tissue-specific requirements and is achieved by formation of macromolecular composites that often share their main molecular components alloyed with minor components. Both, the mechanisms of formation and the final macromolecular organizations depend on the identity of the components and their quantitative contribution. Collagen I is the predominant matrix constituent in many tissues and aggregates with other collagens and/or fibril-associated macromolecules into distinct types of banded fibrils. Here, we studied co-assembly of collagens I and XI, which co-exist in fibrils of several normal and pathologically altered tissues, including fibrous cartilage and bone, or osteoarthritic joints. Immediately upon initiation of fibrillogenesis, the proteins co-assembled into alloy-like stubby aggregates that represented efficient nucleation sites for the formation of composite fibrils. Propagation of fibrillogenesis occurred by exclusive accretion of collagen I to yield composite fibrils of highly variable diameters. Therefore, collagen I/XI fibrils strikingly differed from the homogeneous fibrillar alloy generated by collagens II and XI, although the constituent polypeptides of collagens I and II are highly homologous. Thus, the mode of aggregation of collagens into vastly diverse fibrillar composites is finely tuned by subtle differences in molecular structures through formation of macromolecular alloys.Extracellular matrix aggregates, despite their functional and morphological diversity, often contain the same type of macromolecules as their major constituent. In tendons, for example, large and strongly banded fibrils of variable width are aggregated into bundles that resist extreme tensile forces in one dimension. By contrast, thin fibrils with uniform diameter and spacing are organized into orthogonal sheets forming the translucent corneal stromal matrix that withstands high traction in two dimensions. However, the same protein, i.e. collagen I, is the quantitatively predominant component in both suprastructures (1, 2). The major cartilage collagen is type II, but this protein, too, is common to fibrils with different structures and functions (3, 4). Finally, collagens I and II occur together in fibrocartilage (5), a tissue characterized by a high resistance to both compressive and tensile forces and that contains fibrous bundles in addition to an amorphous extrafibrillar matrix rich in proteoglycans.Collagens I and II are very similar in their molecular structure. They both contain three polypeptides with a central sequence of 1014 amino acids in which strictly every third residue is glycine. In addition, these glycine residues are frequently preceded by hydroxyproline and/or followed by proline. The (Gly-Xaa-Yaa) n sequences are flanked at both ends by short non-periodic sequences, called telopeptide...

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Section: Discussionmentioning

confidence: 99%

Macromolecular Specificity of Collagen Fibrillogenesis

Hansen

Brückner

2003

Journal of Biological Chemistry

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“…144 Type II collagen, the production of which is normally restricted to chondrocytes, is also evident in calcifying intimal lesions. 121,124 In chondrocyte cultures 145 and developing bone, 146 type II collagen is essential for chondrocyte maturation and the presence of type II collagen surrounding chondrocyte-like cells in atherosclerotic plaques suggests a similar mechanism in intimal calcification, although this remains to be directly investigated.…”

Section: Atherosclerotic Calcificationmentioning

confidence: 99%

Collagens in the progression and complications of atherosclerosis

et al. 2009

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Collagens constitute a major portion of the extracellular matrix in the atherosclerotic plaque, where they contribute to the strength and integrity of the fibrous cap, and also modulate cellular responses via specific receptors and signaling pathways. This review focuses on the diverse roles that collagens play in atherosclerosis; regulating the infiltration and differentiation of smooth muscle cells and macrophages; controlling matrix remodeling through feedback signaling to proteinases; and influencing the development of atherosclerotic complications such as plaque rupture, aneurysm formation and calcification. Expanding our understanding of the pathways involved in cell-matrix interactions will provide new therapeutic targets and strategies for the diagnosis and treatment of atherosclerosis.

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“…N-propeptide retention has been correlated with a thin fibril diameter and the authors suggest that these N-propeptides may function in the matrix to regulate fibril growth, intermolecular cross-linking and interaction with extracellular components andlor neighbouring cells. The physiological importance of these collagens has been pointed out in targeted experiments of Co15a2 gene (Andrikopoulos et al, 1995) and Col2a1 gene (Li et al, 1995a), and in homozygous mice for the autosomal recessive chondrodysplasia (Li et al, 1995b). In all cases, homozygous mice died just before or shortly after birth.…”

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confidence: 99%

Collagen Fibrillogenesis during Sea Urchin Development

Lethias

Exposito

Garrone

1997

European Journal of Biochemistry

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The sea urchin 2a fibrillar collagen chain has a unique amino-propeptide structure with several repetitions of a still unknown 140-145-amino-acid, four-Cys module called SURF (for sea urchin fibrillar module). To follow the expression of the amino-propeptide of the 2cr chain and assign a function to this domain, we have overproduced in Escherichiu culi several recombinant proteins corresponding either to the amino-propeptide or to the amino-telopeptide. Monoclonal andor polyclonal antibodies against these recombinant proteins allowed us to observe a similar tissue distribution during the first stages of development. A signal is first observed at the prism stage as intracellular spots in mesenchymal cells. In plutei, immunofluorescence staining is observed around the skeleton spicules and as a thin meshwork surrounding the mesenchymal cells. At the ultrastructural level, and using antibodies against the amino-propeptide, gold particles are observed at the surface of 25 nm thin periodic fibrils. By rotary shadowing, these fibrils show a brush-bottle aspect, exhibiting at their surface numerous periodically distributed thin rods ended by a small globule. These data indicate that the amino-propeptide is maintained during fibrillogenesis.As previously suggested, the retention of the amino-propeptide could play an important role in regulation of the fibril growth. We propose that the important region of this amino-propeptide in the widely encountered 25-nm-diameter fibrils is the short triple-helical segment. The globular part of the amino-propeptide will not only restrict the fibril growth but also interact with other neighbouring components and playing, as suspected from our immunofluorescence studies, a function during the spiculogenesis of the sea urchin embryo.Keywords: sea urchin; collagen ; fibrillogenesis; amino-propeptide.In higher vertebrates, 19 collagen types have been characterized, which from the protein structure and the related gene organization can be divided into several groups (for a recent review, see Prockop and Kivirikko, 1995). One of these comprises the fibrillar collagens which aggregate into the periodic fibers. Five types of fibrillar collagens (types I, 11, 111, V and XI) have been characterized and nine genetically distinct a chains can combine in the formation of the procollagen molecules which can be homotrimeric or heterotrimeric, but also heterotypic (V/XI) (Niyibizi and Eyre, 1989;Prockop and Kivirikko, 1995). Each procollagen molecule is composed of three a chains, each of which contains a perfect triple-helical domain made of an uninterrupted series of Gly-Xaa-Yaa amino acid triplets flanked by two non-collageneous domains, the amino-(N-) and the carboxy-(C-) propeptide. Two short segments, the N-and C-telopeptide respectively, link the N-and the C-propeptide to the central triple-helical domain. During the extracellular maturation of the procollagen molecules, the two propeptide regions are generally removed by the action of two specific proteases (the N-and the C-proteinase), and ...

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Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone.

Cited by 224 publications

References 36 publications

Macromolecular Specificity of Collagen Fibrillogenesis

Macromolecular Specificity of Collagen Fibrillogenesis

Collagens in the progression and complications of atherosclerosis

Collagen Fibrillogenesis during Sea Urchin Development

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