Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.
Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.
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DOI：
10.1002/art.33414
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发表时间：
2012-04
影响因子：
--
通讯作者：
Adarichev, Vyacheslav A.
中科院分区：
文献类型：
--
作者：
Kudryavtseva, Elena;Forde, Toni S.;Pucker, Andrew D.;Adarichev, Vyacheslav A.
类风湿性关节炎（RA）的性别差异是有据可查的，尽管缺乏任何已知的主要RA易感基因映射到性染色体。小鼠15号染色体携带介导蛋白聚糖诱导的关节炎（PGIA）的受性别影响的Pgia 8基因座;同源人类基因座与RA相关。本研究使用Pgia 8同源株来鉴定关节炎性别差异中涉及的基因/机制。使用从患有胶原抗体诱导的关节炎（CAIA）的同源雄性和雌性的爪分离的RNA进行基因表达分析。用RT-PCR证实了数据，并在疾病发作前在小鼠中进行了研究。对表达模式和基因功能的分析用于发现位点特异性和性别影响的签名转录本。我们发现，Pgia 8基因座调节抗体介导的炎症性关节炎不同的男性和女性。在Pgia 8同源雄性中，关节炎严重程度比野生型雄性低30%（p < 0.005），但抗炎作用在野生型和同源雌性中相似。转录组分析表明，12个基因的基因座显着失调关节炎的同源小鼠，这些基因的表达也是性别特异性的。与关节炎严重程度相关性最高的基因包括Cthrc 1、金属蛋白酶Adamts 12、Rspo 2和Syndecan（r=0.87-0.91）。Cthrc 1信使水平与促炎细胞因子IL-1β和IL-6水平也相关。RA中的性别特异性差异与参与软骨降解（Adamts 12）和经典和非经典Wnt信号传导（Cthrc 1，Rspo 2，Sdc 2）的基因的转录调控有关。
Gender 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 (PGIA); homologous human loci are associated with RA. This study uses a Pgia8 congenic strain to identify genes/mechanisms implicated in gender disparities in arthritis. Gene expression analysis was performed using RNA isolated from paws of congenic males and females with collagen antibody-induced arthritis (CAIA). Data were corroborated with RT-PCR and also studied in mice prior to disease onset. Ingenuity Pathways Analysis of the expression patterns and gene functions were 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 anti-inflammatory effect was similar in wild type and congenic females. Transcriptome analysis indicated that twelve genes within the locus were significantly deregulated in arthritic joints of congenic mice; expression of these genes was also gender specific. The genes that correlated the most with arthritis severity include collagen triple helix repeat containing-1 (Cthrc1), metalloproteinase Adamts12, R-spondyn (Rspo2) and Syndecan (Sdc2) (r=0.87–0.91). The level of Cthrc1 message also correlated with that of pro-inflammatory cytokines IL-1β and IL-6. Gender-specific disparities in RA are linked to transcriptional regulation of genes involved in cartilage degradation (Adamts12) and canonical and non-canonical Wnt signaling (Cthrc1, Rspo2, Sdc2).
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影响因子：
4.5
作者：
Libioulle C;Louis E;Hansoul S;Sandor C;Farnir F;Franchimont D;Vermeire S;Dewit O;de Vos M;Dixon A;Demarche B;Gut I;Heath S;Foglio M;Liang L;Laukens D;Mni M;Zelenika D;Van Gossum A;Rutgeerts P;Belaiche J;Lathrop M;Georges M
通讯作者：
Georges M
影响因子：
5.3
作者：
Etzel, Carol J.;Chen, Wei V.;Amos, Christopher I.
通讯作者：
Amos, Christopher I.
影响因子：
--
作者：
Jawaheer, Damini;Lum, Raymond F.;Criswell, Lindsey A.
通讯作者：
Criswell, Lindsey A.
影响因子：
82.9
作者：
Diarra, Danielle;Stolina, Marina;Schett, Georg
通讯作者：
Schett, Georg
影响因子：
4.8
作者：
Liu, Chuan-ju;Kong, Wei;Di Cesare, Paul E.
通讯作者：
Di Cesare, Paul E.