Short‐Chain Collagen Genes and Their Expression in Cartilage

Olsen, Bjørn R.; Ninomiya, Yoshifumi; Lozano, Guillermina; Konomi, Hiroshi; Gordon, Marion K.; Green, Graham; Parsons, J. R.; Seyer, Jerome M.; Thompson, Hillary; Vasios, George

doi:10.1111/j.1749-6632.1985.tb51162.x

Cited by 17 publications

(4 citation statements)

References 31 publications

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“…Little is known about the downstream targets of PTHrP and Ihh signaling in the growth plate, particularly the consequences at the levels of gene transcription as chondrocytes withdraw from the cell cycle and differentiate to hypertrophic chondrocytes. This differentiation is associated with the transcriptional up-regulation of several genes, such as collagen X, MMP13, VEGF, Cbfa1/Runx2, and down-regulation of others, including collagen II (Olsen et al, 1985;Jimenez et al, 1999;Porte et al, 1999;Zelzer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4 -5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.

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Section: Introductionmentioning

confidence: 99%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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“…This structure is stabilized in the presence of NaDodSO4 by strong noncovalent acid-labile interactions and covalent cross-links to produce y and 13 chains of Mr 194,000 and 124,000. Type IX (10) and X collagen (11) polypeptides are about half the size of the proa chains oftypes I, II, and III procollagens. In addition, several other low molecular weight collagens have been isolated and partially characterized (12)(13)(14), and collagenous sequences are also found in several other proteins such as Clq (3), acetylcholinesterase (3), and conglutinin (15).…”

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confidence: 99%

Partial characterization of a low molecular weight human collagen that undergoes alternative splicing.

Pihlajaniemi¹,

Myllylä²,

Seyer³

et al. 1987

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

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A cDNA library prepared from RNA isolated from a cultured human tumor cell line, HT-1080, was screened with a mouse cDNA clone coding for part of the -Gly-Xaa-Yaadomain of the a2(IV) collagen chain. Four overlapping cDNA clones were characterized that coded for a low molecular weight human collagen. The cDNA clones did not, however, code for the short-chain collagens, types IX and X. The amino acid sequences derived from the clones resembled type IV collagen in that there were short interruptions in the repeating -Gly-Xaa-Yaa-sequence. The noncollagenous, carboxyl-terminal domain was, however, much shorter and contained only 18 amino acid residues. Interestingly, one of the cDNA clones contained an additional 36 nucleotides not found in an overlapping clone. The 36 nucleotides encoded four -Gly-Xaa-Yaarepeats without changing the reading frame. Nuclease S1 mapping demonstrated that the difference between the clones was due to existence of two different mRNAs. A synthetic 24-residue peptide corresponding to the last two -Gly-Xaa-Yaatriplets and the entire carboxyl-terminal domain was used to generate polyclonal antibodies. Electrophoretic transfer blot analysis of HT-1080 cells and normal human skin fibroblasts identified two polypeptides, Mr 67,000 and Mr 62,000, that were sensitive to bacterial collagenase.The collagens are major structural components of the extracellular matrix. In vertebrates they consist of 10 or more genetically distinct protein types and at least 22 genes code for their constituent a chains (1-3). The fibrillar collagen types I, II, III, and V are synthesized as precursor proa chains that include a central collagen domain of about 1000 amino acids with a repeating sequence of -Gly-Xaa-Yaatriplets. In addition, the proa chains contain amino-and carboxyl-terminal propeptides that are cleaved after the chains are assembled into procollagen trimers. Type IV collagen is specific to basement membranes and forms a network-like structure. In contrast to fibrillar collagens, type IV collagen has a somewhat larger -Gly-Xaa-Yaa-domain that is interrupted at several sites (1-3).Recently, several additional nonfibrillar collagens have been identified in various connective tissues. In type VI collagen, the collagen domain comprises only one-third of the protein and large globular domains are present at each end (4). The long-chain collagen or type VII collagen contains an extended triple helical domain (5). The size of type VIII collagen polypeptides is presently controversial. An "interrupted helix" (6) or a "cassette" (7) model describes type VIII collagen as composed of three chains of about Mr 180,000, arranged in a predominantly helical structure, but with interruptions in the helix at approximately one-third and two-thirds the length of the molecule. Furthermore, a recent work by Kapoor et al. (8) describes isolation of two structurally different pepsin-resistant Mr 50,000 polypeptides that were derived from a larger form of type VIII collagen. In an alternative model by Benya and Padilla...

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“…The group includes types IX, X, and XII collagens (2,15). The gene for type IX collagen (16) has only a few 54-bp exons (17), and the gene for the type X collagen has no intervening sequences that interrupt the triple helix coding sequences in the gene (18).…”

Section: Introductionmentioning

confidence: 99%

Gene structure for the alpha 1 chain of a human short-chain collagen (type XIII) with alternatively spliced transcripts and translation termination codon at the 5' end of the last exon.

Tikka

Pihlajaniemi

Henttu

et al. 1988

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

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Two overlapping human genomic clones that encode a short-chain collagen, designated al(XI), were isolated by using recently described cDNA clones. Characterization of the cosmid clones that span w65,000 base pairs (bp) of the 3' end of the gene established several unusual features of this collagen gene. The last exon encodes solely the 3' untranslated region and it begins with a complete stop codon. The 10 adjacent exons vary in size from 27 to 87 bp and two of them are 54 bp. Therefore, the al-chain gene of type XIII collagen has some features found in genes for fibrillar collagens but other features that are distinctly different. Previous analysis of overlapping cDNA clones and nuclease S1 mapping of mRNAs indicated one alternative splicing site causing a deletion of 36 bp from the mature mRNA. The present study showed that the 36 bp is contained within the gene as a single exon and also that the gene has a 45-bp -Gly-Xaa-Xaa-repeat coding exon not found in the cDNA clones previously characterized. Nuclease S1 mapping experiments indicated that this 45-bp exon is found in normal human skin fibroblast mRNAs. Accordingly, the data demonstrate that there is alternative splicing ofat least two exons of the type rl(XHI)-chain gene.The collagen family of proteins constitutes the major structural supportive elements of the body. There are at least 13 types of collagens that can be divided into three major groups based on similarities in their protein and gene structure: the fibrillar collagens, the large nonfibrillar collagens, and the short-chain collagens (1-3).The fibrillar collagens are a highly homologous group of proteins that share features such as a similar biosynthetic pathway, a common size for a chains (Mr, >95,000), and a large uninterrupted triple-helical domain with a repeating -Gly-Xaa-Xaa-amino acid sequence. Based on these features, the group of fibrillar collagens includes types I, II, III, and V. Type XI collagen also appears to belong to this group (4). The fibrillar collagens also share an unusual and highly conserved gene structure in terms of the intron-exon pattern. Most of the exons encoding the triple-helical domain begin with a complete codon for glycine. Also, the exon sizes have a characteristic 54-base-pair (bp) pattern with most of the exons being 54, 108, and 162 bp and the rest being 45 or 99 bp. In addition, the sizes of specific exons are highly conserved among types I, II, III, and V collagen genes both within a given species and across a broad spectrum of species (5-8).The large nonfibrillar collagens are characterized by a chains of Mr >95,000 and by interruptions in the repeating -Gly-Xaa-Xaa-sequences of their triple-helical domains (1,9). This group includes types IV, VI, and VIII collagens. The genes for the type IV collagen al and a2 chains lack the regular 54-bp exon pattern (10-14).The group of short-chain collagens are characterized by a chains of Mr considerably less than 95,000. The group includes types IX, X, and XII collagens (2,15). The gene for type IX colla...

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Short‐Chain Collagen Genes and Their Expression in Cartilage

Cited by 17 publications

References 31 publications

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Partial characterization of a low molecular weight human collagen that undergoes alternative splicing.

Gene structure for the alpha 1 chain of a human short-chain collagen (type XIII) with alternatively spliced transcripts and translation termination codon at the 5' end of the last exon.

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