ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1002

Global Transcriptome Analysis in Osteoarthritic Cartilage Reveals Significant Differential Gene Expression and Associations with Histologic Disease Progression

Matlock A. Jeffries1,2, Madison Donica3, Anand Annan4, Michael Stevenson5, Mary Beth Humphrey6,7, Judith A. James6,8 and Amr H. Sawalha9, 1Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Arthritis & Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 3College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 4Pathol;ogy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 5Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 6Rheumatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 7Rheumatology/Immunology/Arthritis Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 8Clinical Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 9Division of Rheumatology, University of Michigan, Ann Arbor, MI

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Disease Activity, epigenetics and osteoarthritis, Gene Expression, RNA

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Biology and Pathology of Bone and Joint: Cartilage, Synovium and Osteoarthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Osteoarthritis (OA) is the leading cause of chronic disability affecting 40% of individuals over the age of 70 and costing $128 billion annually in the US alone.  Little is known regarding changes in gene expression that occur regionally within these affected joints. Herein, we perform RNA-seq analysis of eroded and intact cartilage from human OA, and correlate transcript levels with histopathologic disease severity.

Methods: Six femoral heads were obtained at the time of hip arthroplasty for primary OA.  Articular cartilage tissue samples were dissected from grossly affected and grossly normal areas of the same joints, flash frozen in liquid nitrogen, and RNA was extracted.  A portion of these samples were also histologically examined for OA severity using modified Mankin scoring.  Following confirmation of RNA quality (RIN value ≥6), samples were sequenced with the Illumina TruSeq system on a MiSeq sequencer.  Raw data were analyzed and mapped using the GeneSifter software package.  Genes with GeneSifter quality score <1.0 were excluded.  For categorical analysis, EdgeR p≤0.01 with Benjamini-Hochberg q≤0.1 and expression ratios ≤0.83 or ≥1.2 between affected and normal tissues were considered significant.  For correlations with histologic score, Pearson’s r>0.75 or <-0.75 with p≤0.05 were considered significant. Gene ontology and pathway analysis was performed using the Ingenuity IPA platform.

Results: Categorical analysis identified 43 overexpressed and 313 underexpressed genes in eroded compared to intact cartilage.  Both under- and overexpressed genes were overrepresented in the fibroblastic growth factor (FGF) signaling pathway (p=0.004).  FGFR2 demonstrated an eroded to intact cartilage expression ratio of 0.46, was highly inversely correlated with OA histologic score severity (r=0.92), and is known to be hypermethylated in eroded OA cartilage. The WNT pathway genes, WNT11 (ratio 0.27) and WNT9A (ratio 0.45), and the STAT3 pathway was also overrepresented, including both under- and overexpressed genes (p=0.001).  A top predicted upstream regulator in differentially expressed genes was mir-9 (p=0.005), known to be associated with metalloproteinase production. Further, we identified 176 genes positively and 1591 genes inversely correlated with histopathologic score.  Among these, the NFAT pathway was highly overrepresented, including both positively and inversely correlated genes (24, p=0.002).  The RIG-I innate immunity pathway was also overrepresented among inversely correlated genes (p=0.008), as were several genes related to chromatin remodeling (overall p=0.009: HDAC1, r=-0.89, MECP2 r=-0.78, RBBP4 r=-0.82, SAP130 r=-0.81, SIN3A r=-0.80). 

Conclusion: Using RNA-seq we detected significant changes in gene expression in eroded compared to intact OA cartilage, as well as expression changes correlated with histologic disease progression in OA.  Our data strongly suggest involvement of several signaling pathways, many of which are potential therapeutic targets for OA.  This work reinforces the heterogeneity of the disease process and provides novel insights into OA pathogenesis.


Disclosure:

M. A. Jeffries,
None;

M. Donica,
None;

A. Annan,
None;

M. Stevenson,
None;

M. B. Humphrey,
None;

J. A. James,
None;

A. H. Sawalha,
None.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/global-transcriptome-analysis-in-osteoarthritic-cartilage-reveals-significant-differential-gene-expression-and-associations-with-histologic-disease-progression/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology