OpenLB
Open Library of Bioscience
Advanced Search
Nature communications
06 10, 2016;7 11849.

Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes.

Rizi Ai, Deepa Hammaker, David L Boyle, Rachel Morgan, Alice M Walsh, Shicai Fan, Gary S Firestein, Wei Wang
Author Information
  1. Rizi Ai: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  2. Deepa Hammaker: Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  3. David L Boyle: Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  4. Rachel Morgan: Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  5. Alice M Walsh: Janssen Research and Development, 1400 McKean Road, Spring House, Pennsylvania 19477, USA.
  6. Shicai Fan: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  7. Gary S Firestein: Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
  8. Wei Wang: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA.
PMID: 27282753 DOI: 10.1038/ncomms11849

Abstract

Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients.

References

  1. Rheumatology (Oxford). 2015 Oct;54(10 ):1890-6 [PMID: 26070937]
  2. Nat Med. 2009 Dec;15(12):1414-20 [PMID: 19898488]
  3. Methods Mol Med. 2007;135:365-75 [PMID: 17951672]
  4. Genome Res. 2013 Sep;23(9):1522-40 [PMID: 23804400]
  5. Genome Biol. 2014 Apr 01;15(4):r54 [PMID: 24690455]
  6. Arthritis Res Ther. 2003;5(6):R352-60 [PMID: 14680510]
  7. J Autoimmun. 2013 Mar;41:6-16 [PMID: 23306098]
  8. Arthritis Rheum. 2002 Aug;46(8):2034-8 [PMID: 12209505]
  9. Arthritis Res Ther. 2011;13(6):R204 [PMID: 22151924]
  10. Arthritis Rheumatol. 2015 Jul;67(7):1978-80 [PMID: 25808728]
  11. Hum Mol Genet. 2000 Nov 1;9(18):2651-63 [PMID: 11063724]
  12. Poult Sci. 1997 Jan;76(1):96-104 [PMID: 9037695]
  13. Medicine (Baltimore). 2014 Jan;93(1):1-10 [PMID: 24378738]
  14. Nat Rev Rheumatol. 2014 Feb;10(2):72-4 [PMID: 24418763]
  15. Ann Rheum Dis. 2010 Jul;69(7):1298-304 [PMID: 20421343]
  16. Arthritis Rheum. 2010 Sep;62(9):2569-81 [PMID: 20872595]
  17. Cell. 2013 May 23;153(5):1149-63 [PMID: 23664763]
  18. Science. 2007 Feb 16;315(5814):952-3 [PMID: 17303744]
  19. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39 [PMID: 22473917]
  20. Nature. 2015 Jul 9;523(7559):212-6 [PMID: 26030523]
  21. Bull Hosp Jt Dis (2013). 2013;71 Suppl 1:S33-40 [PMID: 24219039]
  22. PLoS One. 2015 Apr 22;10(4):e0124254 [PMID: 25901943]
  23. Ann Rheum Dis. 2013 Jan;72(1):110-7 [PMID: 22736089]
  24. Clin Exp Rheumatol. 2012 Jul-Aug;30(4 Suppl 73):S50-5 [PMID: 23079199]
  25. Am J Pathol. 1996 Nov;149(5):1607-15 [PMID: 8909250]
  26. Nature. 2013 Aug 22;500(7463):477-81 [PMID: 23925113]
  27. Genome Med. 2013 Apr 30;5(4):40 [PMID: 23631487]
  28. Nature. 2003 May 15;423(6937):356-61 [PMID: 12748655]
  29. Int J Mol Med. 2002 Jul;10(1):41-8 [PMID: 12060849]
  30. Nat Rev Rheumatol. 2014 Feb;10(2):77-88 [PMID: 24217582]
  31. Nucleic Acids Res. 2013 Oct;41(18):8503-14 [PMID: 23887936]
  32. Subcell Biochem. 2013;61:455-78 [PMID: 23150263]
  33. Genes Immun. 2007 Sep;8(6):480-91 [PMID: 17568789]
  34. Arthritis Res Ther. 2014;16(3):114 [PMID: 25167330]

Grants

  1. R01 AI070555/NIAID NIH HHS
  2. R01 AR065466/NIAMS NIH HHS
  3. T32 AR064194/NIAMS NIH HHS

MeSH Term

Arthritis, Rheumatoid
Cluster Analysis
DNA Methylation
Databases as Topic
Female
Fibroblasts
Gene Expression Profiling
Gene Expression Regulation
Hip
Humans
Interleukin-6
Joints
Knee
Middle Aged
Organ Specificity
Osteoarthritis
Principal Component Analysis
Reproducibility of Results
Signal Transduction
Synoviocytes
Transcriptome

Chemicals

Interleukin-6
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000338 (Joint-specific DNA transcriptome signatures in rheumatoid arthritis [RNA-seq])

Word Cloud

Similar Articles

Cited By