Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease.

Fässler, Reinhard; Schnegelsberg, Patrick N.J.; Dausman, Jessica; Shinya, Takashi; Muragaki, Yasuteru; McCarthy, Megan; Olsen, Bjørn R.; Jaenisch, Rudolf

doi:10.1073/pnas.91.11.5070

Cited by 267 publications

(187 citation statements)

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“…Collagen IX was the first of many cartilage structural proteins to be investigated using targeted gene manipulation in mice (10,43). These original studies revealed the role of collagen IX in maintaining cartilage integrity and were predictive of the degenerative changes in patients with multiple epiphyseal dysplasia (4).…”

Section: Discussionmentioning

confidence: 99%

“…These alterations appear to affect chondrocyte survival, leading to growth retardation and short stature (8,9). At later stages in juvenile and adult mice the phenotype becomes attenuated but at 6 months an osteoarthritis-like phenotype develops, characterized by proteoglycan depletion and loss of intact collagen II (10). Hence, alteration of collagen IX homeostasis affects the ECM architecture, the differentiation and survival of chondrocytes, and the matrix-chondrocyte cross-talk.…”

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confidence: 99%

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Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome

Brachvogel

Zaucke

Dave

et al. 2013

Journal of Biological Chemistry

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Background: Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Results: Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Conclusion: Matrilin-4, collagen XII, thrombospondin-4, fibronectin, ␤ig-h3, and epiphycan are components of the in vivo collagen IX interactome. Significance: We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome

Brachvogel

Zaucke

Dave

et al. 2013

Journal of Biological Chemistry

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“…Experiments were performed with C57BL/6 wild-type BACCol10a1-LacZ transgenic (15) or Col9a1-deficient mice, (16) in accordance with the animal ethics guidelines of the Murdoch Children's Research Institute and German law.…”

Section: Micementioning

confidence: 99%

Sorting of growth plate chondrocytes allows the isolation and characterization of cells of a defined differentiation status

Belluoccio¹,

Etich²,

Rosenbaum³

et al. 2010

Journal of Bone and Mineral Research

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Axial growth of long bones occurs through a coordinated process of growth plate chondrocyte proliferation and differentiation. This maturation of chondrocytes is reflected in a zonal change in gene expression and cell morphology from resting to proliferative, prehypertrophic, and hypertrophic chondrocytes of the growth plate followed by ossification. A major experimental limitation in understanding growth plate biology and pathophysiology is the lack of a robust technique to isolate cells from the different zones, particularly from small animals. Here, we report on a new strategy for separating distinct chondrocyte populations from mouse growth plates. By transcriptome profiling of microdissected zones of growth plates, we identified novel, zone-specific cell surface markers and used these for flow cytometry and immunomagnetic cell separation to quantify, enrich, and characterize chondrocytes populations with respect to their differentiation status. This approach provides a novel platform to study cartilage development and characterize mouse growth plate chondrocytes to reveal unique cellular phenotypes of the distinct subpopulations within the growth plate. ß

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“…A second promoter, located between exons 6 and 7, is utilized in other tissues to express a short form of the ␣1(IX) chain that lacks the large NC4 domain (19,20). Interestingly, mice that lack type IX collagen develop normally but exhibit a late-onset form of joint degeneration similar to osteoarthritis, suggesting a stabilizing role for type IX collagen in cartilage (21,22). …”

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confidence: 99%

Regulation of Human COL9A1 Gene Expression

Zhang¹,

Jimenez

Stokes

2003

Journal of Biological Chemistry

111

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The COL9A1 gene contains two promoter regions, one driving expression of a long ␣1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream). To determine how the chondrocyte-specific expression of the COL9A1 gene is regulated, we have begun to characterize the upstream chondrocyte-specific promoter region of the human COL9A1 gene. Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells. Inclusion of the first intron had no effect on promoter activity. In transienttransfection analyses with promoter deletion constructs, it was found that full promoter activity in RCS cells depended on the region from ؊560 bp to ؉130 bp relative to the transcriptional start site (؉1). Sequence analysis of the region from ؊890 bp to the transcriptional start predicted five putative SOX/Sry-binding sites. Mutation analysis revealed that two of three putative SOX/Sry binding sites within the ؊560 to ؉130 bp region are responsible for most of the COL9A1 promoter activity in RCS cells. Co-transfection experiments with a SOX9 expression plasmid revealed that a construct containing the five putative SOX/Sry-binding sites was transactivated 20-to 30-fold in both HTB and NIH/3T3 cells. Further co-transfection experiments showed that two of the SOX/Sry-binding sites located within the ؊560 to ؉130 bp region were required for full transactivation. However, mutation and deletion analyses indicated that a region from ؊560 to ؊357 bp, which does not contain any other conspicuous SOX9 sites, is also important for full promoter activity. DNA-protein binding assays and super-shift analysis revealed that SOX9 can form a specific complex with one of the SOX/Sry-binding sites with in the ؊560 to ؉130 region.The chondrocyte is responsible for the precise production of several different types of cartilage tissues in the developing vertebrate; including growth plate cartilage, articular cartilage, and the cartilage of the ear and trachea. In each of these situations, the elaboration of a complex and extensive extracellular matrix, which is the main functional component of cartilaginous tissues, is crucial. The expression of extracellular matrix molecules by chondrocytes must, therefore, be tightly and coordinately controlled at the level of both synthesis and degradation to ensure that the matrix is properly constructed and maintained. Part of this control occurs at the level of the regulation of chondrocyte-specific gene expression. The best studied gene in this regard is the COL2A1 gene, which gives rise to the main fibrillar collagen in the cartilage matrix. The expression of the COL2A1 gene is controlled through transcription factors that interact with both the promoter and the chondrocyte-specific enhancer located within the first intron (1-4). Recent work has shown that both positive and negative factors interact with the COL2A1 g...

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Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease.

Cited by 267 publications

References 31 publications

Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome

Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome

Sorting of growth plate chondrocytes allows the isolation and characterization of cells of a defined differentiation status

Regulation of Human COL9A1 Gene Expression

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