First comprehensive mapping of cartilage transcripts to the human genome

Yager, Tom; Dempsey, Adam A.; Tang, Hong-Chang; Stamatiou, Dimitri; Chao, Samuel T.; Marshall, K. W.; Liew, Choong‐Chin

doi:10.1016/j.ygeno.2004.05.006

Cited by 22 publications

(15 citation statements)

References 47 publications

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“…Preferential chromosomal location for up-or down-regulated genes. Among the most highly represented chromosomal regions, a 2 test was used to search for significant differences between the number of dysregulated genes observed per chromosome or chromosomal location and the number of genes expected on the entire array (55). Eight regions were then identified as significant.…”

Section: Chemotaxis Assaymentioning

confidence: 99%

Microarrays Reveal Distinct Gene Signatures in the Thymus of Seropositive and Seronegative Myasthenia Gravis Patients and the Role of CC Chemokine Ligand 21 in Thymic Hyperplasia

Panse

Cizeron-Clairac

Bismuth

et al. 2006

The Journal of Immunology

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Myasthenia gravis (MG) is an autoimmune disease mainly caused by antiacetylcholine receptor autoantibodies (seropositive (SP) disease) or by Abs against unknown autoantigenic target(s) (seronegative (SN) disease). Thymectomy is usually beneficial although thymic hyperplasia with ectopic germinal centers is mainly observed in SP MG. To understand the role of thymus in the disease process, we compared the thymic transcriptome of non-MG adults to those of SP patients with a low or high degree of hyperplasia or SN patients. Surprisingly, an overexpression of MHC class II, Ig, and B cell marker genes is observed in SP but also SN MG patients. Moreover, we demonstrate an overexpression of CXCL13 in all MG thymuses leading probably to the generalized B cell infiltration. However, we find different chemotactic properties for MG subgroups and, especially, a specific overexpression of CCL21 in hyperplastic thymuses triggering most likely ectopic germinal center development. Besides, SN patients present a peculiar signature with an abnormal expression of genes involved in muscle development and synaptic transmission, but also genes implicated in host response, suggesting that viral infection might be related to SN MG. Altogether, these results underline differential pathogenic mechanisms in the thymus of SP and SN MG and propose new research areas.

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Section: Chemotaxis Assaymentioning

confidence: 99%

Microarrays Reveal Distinct Gene Signatures in the Thymus of Seropositive and Seronegative Myasthenia Gravis Patients and the Role of CC Chemokine Ligand 21 in Thymic Hyperplasia

Panse

Cizeron-Clairac

Bismuth

et al. 2006

The Journal of Immunology

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“…However, the molecular changes associated with OA in these tissues have only recently begun to be elucidated (for review, see refs. [3][4][5][6][7][8].…”

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confidence: 99%

Inverse relationship between matrix remodeling and lipid metabolism during osteoarthritis progression in the STR/ORT mouse

Watters¹,

Cheng²,

Pickarski³

et al. 2007

Arthritis & Rheumatism

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Objective. The biologic changes associated with osteoarthritis (OA) are incompletely understood. The aim of this study was to elucidate the molecular mechanisms underlying OA progression in an STR/Ort murine model of spontaneous disease.Methods. Global patterns of gene expression were assessed using microarray analysis of articular cartilage/subchondral bone from the tibial plateaus of STR/Ort mice at 3, 9, and 12 months of age. The age-dependent severity of osteophyte formation and extent of cartilage damage were determined in the corresponding femurs using microfocal computed tomography and the Mankin histologic scoring system. Pathway analysis was used to identify the functions of genes associated with OA progression, and changes in gene expression were confirmed using immunohistochemistry.Results. Six hundred twenty-one genes were associated with both osteophyte formation and cartilage damage in the STR/Ort joints. Genes involved in the development/function of connective tissue and in lipid metabolism were most significantly enriched and regulated during disease progression. Genes directly interacting with peroxisome proliferator-activated receptor ␣ (PPAR␣)/PPAR␥ were down-regulated, whereas those genes involved with connective tissue remodeling were up-regulated during disease progression. Associations of down-regulation of myotubularinrelated phosphatase 1 (a phosphoinositide 3-phosphatase involved in lipid signaling) and up-regulation of biglycan (a member of the small leucine-rich protein family known to modulate osteoblast differentiation and matrix mineralization) with OA progression were confirmed by immunohistochemistry.Conclusion. Since adipogenesis and osteogenesis are inversely related in the developing skeletal tissue, these results suggest that a shift in the differentiation of mesenchymal cells from adipogenesis toward osteogenesis is a component of the OA pathophysiologic processes occurring in the tibial plateau joints of STR/Ort mice.

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“…HDACs show a varied tissue distribution, and mapping of cartilage transcripts shows evidence for expression of many HDACs in this tissue [12]. The recent work from Young and colleagues [1] shows the effective use of HDAC inhibitors for decreasing metalloproteinase expression in cartilage and demonstrates that the paradigm of inhibition of histone deacetylation leading to gene silencing is not absolute.…”

mentioning

confidence: 99%

Untitled

Mort

2005

Arthritis Res Ther

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155 ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs; bp = base pairs; HDAC = histone deacetylase; MMP = matrix metalloproteinase; TIMP = tissue inhibitor of metalloproteinases.Available online http://arthritis-research.com/contents/7/4/155 AbstractIncreased expression of metalloproteinases is a fundamental aspect of arthritis pathology and its control is a major therapeutic objective. In cartilage cultured in the presence of the cytokines interleukin-1 and oncostatin M, chondrocytes produce enhanced levels of metalloproteinases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMP (matrix metalloproteinase) families, resulting in the degradation of aggrecan and collagen. The histone deacetylase inhibitors trichostatin A and butyrate were shown to drastically reduce expression of these enzymes relatively selectively, with concomitant inhibition of breakdown of matrix components. This family of enzymes is therefore a promising target for therapeutic intervention.Proteolytic activity in articular cartilage is central to joint destruction in arthritis. Proteinase expression is well known to be modulated by cytokines, intracellular signaling, and transcription factor action, but recent work by Young and colleagues [1] indicates that there is significantly more to this process than has been generally believed.The human genome is packed in a matrix of histones that shield it from transcription by RNA polymerase II. The basic unit of chromatin is the nucleosome core particle, which consists of 147 bp of DNA wound 1.7 times around a histone octamer composed of two copies each of four histone partners (H2A, H2B, H3, and H4). The core particles are separated by a 10-to 60-bp linker region and the resulting 'beads-on-a-string' are further condensed into thicker fibers, which make up chromatin [2].While structural studies suggested the nucleosome to be a stable particle, it is now clear that in vivo it is much more dynamic [3]; histone units can be exchanged and the whole complex is able to slide along the DNA in an ATP-dependent mechanism through the action of members of the Swi2/Snf2 family of ATPases. In addition to a conserved globular core protein region, each histone molecule contains an N-terminal tail rich in basic residues, which project beyond the surrounding DNA. In the case of H3 and H4, specific lysine sidechains undergo acetylation, through the action of histone acetyltransferases, by way of acetyl coenzyme A, a step which is associated with transcriptional activation. These modifications can be reversed by histone deacetylases (HDACs), of which there are four families [4].Three of the families (I, II, and IV) are zinc-dependent enzymes, catalytically resembling the metalloproteinases, but family III (the recently discover SIR2 enzymes) uses a completely different mechanism depending on NAD + (oxidized nicotinamide-adenine dinucleotide) as a cofactor [5]. The members of family II are of particular importance because they are modular proteins with binding ...

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First comprehensive mapping of cartilage transcripts to the human genome

Cited by 22 publications

References 47 publications

Microarrays Reveal Distinct Gene Signatures in the Thymus of Seropositive and Seronegative Myasthenia Gravis Patients and the Role of CC Chemokine Ligand 21 in Thymic Hyperplasia

Microarrays Reveal Distinct Gene Signatures in the Thymus of Seropositive and Seronegative Myasthenia Gravis Patients and the Role of CC Chemokine Ligand 21 in Thymic Hyperplasia

Inverse relationship between matrix remodeling and lipid metabolism during osteoarthritis progression in the STR/ORT mouse

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