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Increased synovial expression of nuclear receptors correlates with protection in pristane-induced arthritis: a possible novel genetically regulated homeostatic mechanism.

Max, Brenner; Linge, Carl Petrus LU ; Li, Wentian and Gulko, Pércio S. (2011) In Arthritis and Rheumatism 63(10). p.29-2918
Abstract
OBJECTIVE: To use microarray analyses of gene expression to characterize the synovial molecular pathways regulated by the arthritis regulatory locus Cia25 and to determine how it operates to control disease severity and joint damage.
METHODS: Synovial tissues from DA rats and DA.ACI(Cia25) rats obtained 21 days after induction of pristane-induced arthritis were used for RNA extraction and hybridization to Illumina RatRef-12 Expression BeadChips (22,228 genes). Genes with a P value≤0.01 and a fold difference in expression≥1.5 between DA rats and DA.ACI(Cia25) rats were considered significant.
RESULTS: Interleukin-1β (IL-1β) (7.4-fold), IL-6 (67-fold), Ccl2, Cxcl10, Mmp3, Mmp14, and innate immunity genes were expressed at increased... (More)
OBJECTIVE: To use microarray analyses of gene expression to characterize the synovial molecular pathways regulated by the arthritis regulatory locus Cia25 and to determine how it operates to control disease severity and joint damage.
METHODS: Synovial tissues from DA rats and DA.ACI(Cia25) rats obtained 21 days after induction of pristane-induced arthritis were used for RNA extraction and hybridization to Illumina RatRef-12 Expression BeadChips (22,228 genes). Genes with a P value≤0.01 and a fold difference in expression≥1.5 between DA rats and DA.ACI(Cia25) rats were considered significant.
RESULTS: Interleukin-1β (IL-1β) (7.4-fold), IL-6 (67-fold), Ccl2, Cxcl10, Mmp3, Mmp14, and innate immunity genes were expressed at increased levels in DA rats and at significantly lower levels in DA.ACI(Cia25) congenic rats. DA.ACI(Cia25) rats had increased expression of 10 nuclear receptor (NR) genes, including those known to interfere with NF-κB activity and cytokine expression, such as Lxra, Pparg, and Rxrg. DA.ACI(Cia25) rats also had increased expression of NR targets, suggesting increased NR activity. While Vdr was not differentially expressed, a Vdr expression signature was detected in congenic rats, along with up-regulation of mediators of vitamin D synthesis.
CONCLUSION: This is the first description of the association between increased synovial levels of NRs and arthritis protection. The expression of NRs was inversely correlated with the expression of key mediators of arthritis, suggesting reciprocally opposing effects either via NF-κB or at the genomic level in the synovial tissue. We consider that the NR signature may have an important role in maintaining synovial homeostasis and an inflammation-free tissue. These processes are regulated by the Cia25 gene and suggest a new function for this gene. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
in
Arthritis and Rheumatism
volume
63
issue
10
pages
29 - 2918
publisher
John Wiley & Sons
external identifiers
  • scopus:80053516910
ISSN
1529-0131
DOI
language
English
LU publication?
no
id
82fb57bf-cd3d-4cf9-a813-0c70847aa30c
date added to LUP
2018-03-29 13:20:09
date last changed
2018-05-29 10:09:21
@article{82fb57bf-cd3d-4cf9-a813-0c70847aa30c,
  abstract     = {OBJECTIVE: To use microarray analyses of gene expression to characterize the synovial molecular pathways regulated by the arthritis regulatory locus Cia25 and to determine how it operates to control disease severity and joint damage.<br/>METHODS: Synovial tissues from DA rats and DA.ACI(Cia25) rats obtained 21 days after induction of pristane-induced arthritis were used for RNA extraction and hybridization to Illumina RatRef-12 Expression BeadChips (22,228 genes). Genes with a P value≤0.01 and a fold difference in expression≥1.5 between DA rats and DA.ACI(Cia25) rats were considered significant.<br/>RESULTS: Interleukin-1β (IL-1β) (7.4-fold), IL-6 (67-fold), Ccl2, Cxcl10, Mmp3, Mmp14, and innate immunity genes were expressed at increased levels in DA rats and at significantly lower levels in DA.ACI(Cia25) congenic rats. DA.ACI(Cia25) rats had increased expression of 10 nuclear receptor (NR) genes, including those known to interfere with NF-κB activity and cytokine expression, such as Lxra, Pparg, and Rxrg. DA.ACI(Cia25) rats also had increased expression of NR targets, suggesting increased NR activity. While Vdr was not differentially expressed, a Vdr expression signature was detected in congenic rats, along with up-regulation of mediators of vitamin D synthesis.<br/>CONCLUSION: This is the first description of the association between increased synovial levels of NRs and arthritis protection. The expression of NRs was inversely correlated with the expression of key mediators of arthritis, suggesting reciprocally opposing effects either via NF-κB or at the genomic level in the synovial tissue. We consider that the NR signature may have an important role in maintaining synovial homeostasis and an inflammation-free tissue. These processes are regulated by the Cia25 gene and suggest a new function for this gene.},
  author       = {Max, Brenner and Linge, Carl Petrus and Li, Wentian and Gulko, Pércio S.},
  issn         = {1529-0131},
  language     = {eng},
  number       = {10},
  pages        = {29--2918},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Increased synovial expression of nuclear receptors correlates with protection in pristane-induced arthritis: a possible novel genetically regulated homeostatic mechanism.},
  url          = {http://dx.doi.org/},
  volume       = {63},
  year         = {2011},
}