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: 16

Adenosine A2A Receptor Diminishes Bone Destruction At Inflamed Sites, in Part, Via Downregulating Semaphorin4D-PlexinB1 Communication Between Osteoclasts and Osteoblasts

Aranzazu Mediero1 and Bruce N. Cronstein2, 1Medicine, Division of Translational Medicine, NYU School of Medicine, New York, NY, 2Internal Medicine, NYU School of Medicine, Division of Rheumatology, New York, NY

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Adenosine receptors, bone metabolism, Inflammation, osteoblasts and osteoclasts

  • 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

Session Type: Abstract Submissions (ACR)

Background/Purpose: Communication between osteoclasts and osteoblasts is essential for bone homeostasis. Semaphorin4D (Sema4D), expressed on the surface of and secreted by osteoclasts, macrophages and T cells, is a potent inhibitor of bone formation; Sema4D binds to its receptor (PlexinB1) on osteoblasts which induces RhoA activation which suppresses osteoblast differentiation by attenuating insulin-like growth factor-1 (IGF-1) signaling. Adenosine, a nucleoside released at sites of injury and hypoxia, modulates cell function by interacting with specific cell-surface receptors (A1R, A2AR, A2BR, A3R). We have recently demonstrated that A2AR stimulation inhibits wear particle-mediated bone destruction and sought to determine whether A2AR-mediated regulation of Sema4D expression might play a role in preventing bone destruction.

Methods: C57Bl/6 mice mice age 6-8 weeks were anesthetized and a 1cm midline sagittal incision was made over the calvaria. 4 mice received no particles (Control), and the rest received 3mg of polyethylene particles (UHMWPE) together with 20µl of saline 0.9% or  CGS21680 1µM (n=4 each) at the surgical site every day. Animals were sacrificed after 14 days and calvaria were prepared for histology. Sema4D expression was studied by RT-PCR and Western Blot in RAW267.4 cell-derived osteoclasts in the presence/absence of CGS21680 and ZM241385 (A2AR antagonist) 1µM each.

Results: As previously described, exposure to UHMWPE particles induce inflammatory infiltration that is significantly decreased in the presence of CGS21680. Exposure to UHMWPE particles significantly increased expression of both Sema4D (224±5cells/Ipf compare to 40±2cells/Ipf in control, p<0.001, n=4) and its receptor PlexinB1 (206±5cells/Ipf compare to 86±4cells/Ipf in control, p<0.001, n=4) on bone surfaces close to inflammatory infiltrates and CGS21680 treatment markedly diminished overexpression of both Sema4D and PlexinB1 (34±3cells/Ipf and 85±3cells/Ipf respectively, p<0.001, n=4). In in vitrostudies, RANKL induced a 2.5±0.1 fold increase in Sema4D mRNA expression (p<0.001. n=4) that is completely blocked by CGS21680 in a protein kinase A-dependent fashion.

Conclusion: Inflammation promotes Sema4D secretion and PlexinB1 activation. Targeting osteoclasts via A2AR activation prevents wear particle-stimulated bone resorption and the inhibition of Sema4D and PlexinB1 expression likely bone resorption by permitting greater osteoblast differentiation and bone formation. Moreover, these results suggest a novel approach to prevent bone resorption in inflammatory arthritis or infectious arthritis.


Disclosure:

A. Mediero,
None;

B. N. Cronstein,

Canfite BioPharma,

1,

NIH, URL Pharma, OSI,

2,

Bristol-Myers Squibb, Novartis, URL, Regeneron, Gismo Therapeutics,

5,

Arthritis Foundation, SLE Foundation,

6,

Patents on use of adenosine receptor antagonists to treat or prevent fibrosis. Multiple other patents.,

.

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

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/adenosine-a2a-receptor-diminishes-bone-destruction-at-inflamed-sites-in-part-via-downregulating-semaphorin4d-plexinb1-communication-between-osteoclasts-and-osteoblasts/

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