Discrete integration of collagen XVI into tissue-specific collagen fibrils or beaded microfibrils

Kassner, Anja; Hansen, Uwe; Miosge, Nicolai; Reinhardt, Dieter P.; Aigner, Thomas; Bruckner‐Tuderman, Leena; Brückner, Peter; Grässel, Susanne

doi:10.1016/s0945-053x(03)00008-8

Cited by 90 publications

(74 citation statements)

References 40 publications

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“…Immunoelectron Microscopy-Fragments of suprastructural aggregates were obtained from human articular cartilage as previously described (26). In brief, slices of cartilage were twice homogenized in 15 volumes of 150 mM NaCl, 2 mM sodium phosphate buffer, pH 7.4 (PBS), containing a mixture of protease inhibitors, and centrifuged at low speed for clarification.…”

Section: Methodsmentioning

confidence: 99%

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Bernardo

Belluoccio

Rowley

et al. 2011

Journal of Biological Chemistry

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Using transcriptome profiling to determine differential gene expression between the permanent mouse articular cartilage and the transient growth plate cartilage, we identified a highly expressed gene, Cilp2, which is expressed differentially by articular chondrocytes. CILP-2 is highly homologous to CILP-1 (cartilage intermediate layer protein 1), which is expressed in the intermediate zone of articular cartilage and has been linked to cartilage degenerative diseases. We demonstrated that Cilp2 has a restricted mRNA distribution at the surface of the mouse articular cartilage during development, becoming localized to the intermediate zone of articular cartilage and meniscal cartilage with maturity. Although the extracellular CILP-2 protein localization is broadly similar to CILP-1, CILP-2 appears to be more localized in the deeper intermediate zone of the articular cartilage extracellular matrix at maturity. CILP-2 was shown to be proteolytically processed, N-glycosylated, and present in human articular cartilage. In surgically induced osteoarthritis in mice, Cilp1 and Cilp2 gene expression was dysregulated. However, whereas Cilp1 expression was increased, Cilp2 gene expression was down-regulated demonstrating a differential response to mechanically induced joint destabilization. CILP-2 protein was reduced in the mouse osteoarthritic cartilage. Ultrastructural analysis also suggested that CILP-2 may be associated with collagen VI microfibrils and thus may mediate interactions between matrix components in the territorial and inter-territorial articular cartilage matrix. mRNA expression analysis indicated that whereas Cilp1 and Cilp2 are expressed most abundantly in cartilaginous tissues, expression can be detected in muscle and heart. During limb development, chondrocytes follow alternative developmental pathways. Chondrocytes that form at the epiphyseal surface of long bones develop into permanent articular chondrocytes and form the smooth articular cartilage necessary for effective weight-bearing and joint movement. The other group of chondrocytes, the transient epiphyseal chondrocytes, are organized into growth plates, and undergo a sequential maturation program from resting cells to proliferative, prehypertrophic, and ultimately hypertrophic end-stage chondrocytes that are replaced with bone during endochondral ossification. Both populations of chondrocytes are critical for the formation of the skeleton and disturbances to normal chondrocyte development and function results in chondrodysplasias (reviewed by Refs. 1-3).One of the important determinants of cartilage function is extracellular matrix (ECM) 3 structure and composition. To identify new ECM determinants of the articular cartilage, we compared the gene expression profile of mouse articular cartilage with growth plate cartilage. These studies revealed that the most highly differentially expressed cDNA on the array was a Riken clone that corresponded to Cilp2 (cartilage intermediatelayer protein, isoform 2), recently reported as a product of cartilage c...

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Section: Methodsmentioning

confidence: 99%

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Bernardo

Belluoccio

Rowley

et al. 2011

Journal of Biological Chemistry

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“…Samples were doubly immunostained with an antiserum against ␣6(VI)C1 domain and a monoclonal antibody against collagen VI (AF6210, Acris Antibodies), and colloidal gold-labeled secondary antibodies of different sizes were analyzed with transmission electron microscopy as described (26).…”

Section: Methodsmentioning

confidence: 99%

Three Novel Collagen VI Chains, α4(VI), α5(VI), and α6(VI)

Fitzgerald

Rich

Zhou

et al. 2008

Journal of Biological Chemistry

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150

158

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We report the identification of three new collagen VI genes at a single locus on human chromosome 3q22.1. The three new genes are COL6A4, COL6A5, and COL6A6 that encode the ␣4(VI), ␣5(VI), and ␣6(VI) chains. In humans, the COL6A4 gene has been disrupted by a chromosome break. Each of the three new collagen chains contains a 336-amino acid triple helix flanked by seven N-terminal von Willebrand factor A-like domains and two (␣4 and ␣6 chains) or three (␣5 chain) C-terminal von Willebrand factor A-like domains. In humans, mRNA expression of COL6A5 is restricted to a few tissues, including lung, testis, and colon. In contrast, the COL6A6 gene is expressed in a wide range of fetal and adult tissues, including lung, kidney, liver, spleen, thymus, heart, and skeletal muscle. Antibodies to the ␣6(VI) chain stained the extracellular matrix of human skeletal and cardiac muscle, lung, and the territorial matrix of articular cartilage. In cell transfection and immunoprecipitation experiments, mouse ␣4(VI)N6-C2 chain co-assembled with endogenous ␣1(VI) and ␣2(VI) chains to form trimeric collagen VI molecules that were secreted from the cell. In contrast, ␣5(VI)N5-C1 and ␣6(VI)N6-C2 chains did not assemble with ␣1(VI) and ␣2(VI) chains and accumulated intracellularly. We conclude that the ␣4(VI)N6-C2 chain contains all the elements necessary for trimerization with ␣1(VI) and ␣2(VI). In summary, the discovery of three additional collagen VI chains doubles the collagen VI family and adds a layer of complexity to collagen VI assembly and function in the extracellular matrix.Collagen VI is an extracellular component that is present in virtually all connective tissues, where it forms abundant and structurally unique microfibrils in close association with basement membranes. Collagen VI interacts with a range of ECM 2 components. However, its precise role is not clearly understood. Several recent studies have suggested that collagen VI functions to anchor the basement membrane to the pericellular matrix in muscle (1-3). Other data suggest a role for collagen VI in cell signaling and cell migration (4, 5).Three genetically distinct collagen VI chains, ␣1(VI), ␣2(VI), and ␣3(VI), encoded by the COL6A1, COL6A2, and COL6A3 genes were first described more than 20 years ago (6 -8). The COL6A1 and COL6A2 genes are located in tandem on chromosome 21q22.3. The ␣1(VI) and ␣2(VI) chains are similar in size and domain structure. They contain a short 335-or 336-amino acid triple helix with a glycine triplet repeat motif that is characteristic of all collagens. Flanking the triple helix are domains homologous to the A-type domains found in von Willebrand factor (VWA domains). ␣1(VI) and ␣2(VI) contain one VWA domain N-terminal to the triple helix (N1) and two VWA domains on the C-terminal flank of the helix (C1 and C2). In contrast, the ␣3(VI) chain, encoded by the COL6A3 gene on 2q37.3, is much larger with 10 N-terminal (N1-N10), two C-terminal VWA domains (C1 and C2), and several other identifiable types of domains at the C terminus (C3-C5).A...

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“…72). Fibrillin-1 is associated with type XVI collagen in the dermis (but not in cartilage), and other proteins such as versican, fibulin, matrix-associated glycoprotein (MAGP)-1, MAGP-2 and emilin ( Refs 73,74,75,76). The microfibril structures that are formed have been divided into essentially three types on the basis of structure and appearance -oxytalan, elaunin and elastic -which differ in the relative amounts of elastin (from lowest to highest, respectively).…”

Section: Glycoproteinsmentioning

confidence: 99%

Chronic tendon pathology: molecular basis and therapeutic implications

Riley

2005

Expert Rev. Mol. Med.

103

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Tendons are frequently affected by chronic pain or rupture. Many causative factors have been implicated in the pathology, which until relatively recently was under-researched and poorly understood. There is now a greater knowledge of the molecular basis of tendon disease. Most tendon pathology (tendinopathy) is associated with degeneration, which is thought to be an active, cell-mediated process involving increased turnover and remodelling of the tendon extracellular matrix. Degradation of the tendon matrix is mediated by a variety of metalloproteinase enzymes, including matrix metalloproteinases and 'aggrecanases'. Neuropeptides and other factors released by stimulated cells or nerve endings in or around the tendon might influence matrix turnover, and could provide novel targets for therapeutic intervention.Tendons are dense, fibrous connective tissues that connect muscle to bone and are essential for the transmission of force and the generation of movement at a joint. They are highly ordered composite materials consisting of collagens, proteoglycans and various glycoproteins, many of which have been poorly characterised. Tendon problems such as tendon rupture and chronic tendon pain are common, although the underlying pathology is not well understood and the conditions are often difficult to treat (Ref.

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Discrete integration of collagen XVI into tissue-specific collagen fibrils or beaded microfibrils

Cited by 90 publications

References 40 publications

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Three Novel Collagen VI Chains, α4(VI), α5(VI), and α6(VI)

Chronic tendon pathology: molecular basis and therapeutic implications

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