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Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.

ABSTRACT: Sex disparities in rheumatoid arthritis (RA) are well documented despite the lack of any known major RA susceptibility genes mapped to sex chromosomes. Murine chromosome 15 carries the sex-affected Pgia8 locus that mediates proteoglycan-induced arthritis, and homologous human loci are associated with RA. This study was undertaken to identify genes/mechanisms implicated in sex disparities in arthritis.Gene expression analysis was performed using RNA isolated from the paws of male and female Pgia8-congenic mice with collagen antibody-induced arthritis. Results were corroborated by reverse transcription-polymerase chain reaction, and mice were also studied prior to disease onset. Ingenuity Pathways Analysis of the expression patterns and gene functions was used to discover locus-specific and sex-affected signature transcripts.We found that the Pgia8 locus regulates antibody-mediated inflammatory arthritis differently in males and females. In Pgia8-congenic males, arthritis severity was 30% less (P < 0.005) than in wild-type males, but the antiinflammatory effect was similar in wild-type and congenic females. Transcriptome analysis indicated that 12 genes within the locus were significantly dysregulated in arthritic joints of congenic mice; expression of these genes was also sex specific. The genes that correlated most highly with arthritis severity included those for collagen triple-helix repeat-containing 1 (Cthrc1), metalloproteinase (Adamts12), R-spondin (Rspo2), and syndecan (Sdc2) (r = 0.87-0.91). The level of Cthrc1 message also correlated with that of the genes for the proinflammatory cytokines interleukin-1? and interleukin-6.These results indicate that sex-specific disparities in RA are linked to transcriptional regulation of genes involved in cartilage degradation (Adamts12) and canonical and noncanonical Wnt signaling (Cthrc1, Rspo2, Sdc2).

SUBMITTER: Kudryavtseva E

PROVIDER: S-EPMC3288823 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.

Kudryavtseva Elena E Forde Toni S TS Pucker Andrew D AD Adarichev Vyacheslav A VA

Arthritis and rheumatism 20111017 4

<h4>Objective</h4>Sex disparities in rheumatoid arthritis (RA) are well documented despite the lack of any known major RA susceptibility genes mapped to sex chromosomes. Murine chromosome 15 carries the sex-affected Pgia8 locus that mediates proteoglycan-induced arthritis, and homologous human loci are associated with RA. This study was undertaken to identify genes/mechanisms implicated in sex disparities in arthritis.<h4>Methods</h4>Gene expression analysis was performed using RNA isolated from ...[more]

PMID: 22005949

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Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.

Publications

Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.

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