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: 148

Microarray Analysis Of  Synovial Specimen of Early Human (CHECK) and Experimental Osteoarthritis to Identify Pathways and Processes Associated with Pathology

Arjen B. Blom1, Peter L. van Lent2, Martijn H. van den Bosch1, Hans Cats3, Frank H.J. van den Hoogen4, Peter M. van der Kraan5 and Wim B. van den Berg6, 1Rheumatology Research & Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 2Rheumatology Research & Advanced Therpeutics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 3Rheumatology, Rheumatology Centre Sint Maartenskliniek, Nijmegen, Netherlands, 4Rheumatology, Rheumatology Centre Sint Maartenskliniek and Radboud university medical center, Ubbergen (Nijmegen), Netherlands, 5Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 6Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Animal models, biopsies, osteoarthritis and synovitis, 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: Genetics and Genomics of Rheumatic Disease I

Session Type: Abstract Submissions (ACR)

Background/Purpose: The majority of osteoarthritis (OA) patients show synovial inflammation, even relatively early during the disease. We used microarray analysis of synovial tissue of early OA patients and of experimental OA, to identify common pathways that determine joint damage in this disease.

Methods: Expression analysis was performed on murine synovial tissue at day 7, day 21 and day 42 in collagenase induced OA (CIOA) and the surgically induced DMM model (destabilization of the medial meniscus). CIOA was induced by intra-articular injection of collagenase, which causes joint instability. From a subpopulation of patients (n= 25) that entered the CHECK Cohort study (Cohort Hip and Cohort Knee) and 7 controls, synovial biopsies were collected at year 0, 2 and 5. CHECK is a prospective 10-year follow-up study on participants with early osteoarthritis-related complaints (less than 6 months before inclusion) initiated by the Dutch Arthritis Association. Kellgren&Lawrence-score (KL) at inclusion was determined (n=18) and follow up measurements were performed at 2 and 5 years. Affymetrix was used for microarray, and pathway analysis was done using DAVID.

Results: Among the genes that were strongly upregulated on all 3 time points after induction of CIOA were MMP-3 (6-fold), MMP-13 (16-fold), MMP-14 (6-fold). Wound healing, phagocytosis, chemotaxis and metalloproteases were significantly enriched, as were the complement pathway, the TLR-, TGFβ, BMP and wnt-signaling pathways. Highly similar results were obtained in the DMM model for OA. However, at day 42 in this model very view genes were still regulated in the synovium compared to other time points or CIOA, indicating that synovial activation differs late between the models. This was underlined by histological examination. All in all, the expression patterns  in experimental OA showed compelling similarities with human OA synovium. Gene expression profiles of control synovia were compared to CHECK synovia. Analysis using DAVID indicated enrichment of several biological processes and signaling pathways, including macrophage presence, cell migration, TGFβ-, BMP- and wnt-signaling. This indicates activation of the synovium in the early OA versus controls. Next we compared synovial tissue of CHECK-patients with radiological damage (KL≥1) with CHECK-patients without joint damage (KL=0). In the top 30 genes that were associated with cartilage damage were MMP-1 (18-fold), MMP-3 (10-fold) and S100A8 (6-fold), all of which have been associated with cartilage damage. FAC analysis further underlined  response to wounding, chemotaxis, innate immune response and metalloproteases to be strongly enriched. In particular,  complement-activation pathway, TGFβ- and BMP-signaling and TLR-activation were striking.

Conclusion: Activation pathways and processes in the two models for OA were highly similar. A major difference lies in the presence of late synovial activation. The data suggest an active role for the synovium in OA pathology, and identifies pathways  that may be involved. Activation of the complement-pathway was strongly associated with damage. In addition, synovial MMP expression was associated with joint damage,  underlining an active role of synovium in OA pathology.


Disclosure:

A. B. Blom,
None;

P. L. van Lent,
None;

M. H. van den Bosch,
None;

H. Cats,
None;

F. H. J. van den Hoogen,
None;

P. M. van der Kraan,
None;

W. B. van den Berg,
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 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/microarray-analysis-of-synovial-specimen-of-early-human-check-and-experimental-osteoarthritis-to-identify-pathways-and-processes-associated-with-pathology/

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