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: 23

Activation of EPAC1/2 Is Essential for Osteoclast Formation By Modulating NFkB Nuclear Translocation and Actin Cytoskeleton Rearrangements

Aranzazu Mediero1, Miguel Perez-Aso2 and Bruce N. Cronstein3, 1Medicine, Division of Translational Medicine, NYU School of Medicine, New York, NY, 2545 1st Ave., New York University, New York City, NY, 3NYU School of Medicine, Division of Rheumatology, New York, NY

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: bone biology, functions, osteoclasts and signal transduction

  • Tweet
  • Email
  • Print
Session Information

Title: Biology and Pathology of Bone and Joint: Osteoclasts, Osteoblasts and Bone Remodeling

Session Type: Abstract Submissions (ACR)

Background/Purpose Bisphosphonates inhibit osteoclast differentiation/function via inhibition of Rap1A isoprenylation and cytoskeletal assembly. As Rap1 is the effector of EPAC proteins (exchange protein directly activated by cAMP), we determined the role of EPAC in osteoclast differentiation.

Methods

Osteoclast differentiation was studied as the number of TRAP+ multinucleated cells following M-CSF/RANKL stimulation of either primary murine or human bone marrow precursors in the presence of the EPAC-selective cAMP analog 8-CPT-cAMP (100nM) and the EPAC inhibitor BFA (10µM). Rap1 activity assay was performed. Signaling events were studied by Western Blot in EPAC1/2 knockdown (lentiviral shRNA for EPAC1 or EPAC2 or scrambled shRNA) RAW264.7 cells. Osteoclast marker expression was studied by RT-PCR. Osteoclast morphological characterization was studied by phalloidin staining.

 Results 8-CPT-cAMP significantly increased osteoclast differentiation whereas BFA inhibited differentiation (113±3% (p<0.05) and 42±2% (p<0.001) of control, respectively, n=6). Rap1 activation was maximal 15 min after RANKL stimulation (136±3% of basal, p<0.001, n=4) whereas silencing of EPAC1/2 diminished activated Rap1 (43±2% and 50±5% of control respectively, p<0.01, n=4) and NFkB translocation. TRAP staining revealed no osteoclast differentiation in EPAC1/2 KO cells. Cathepsin K, NFATc1 and Osteopontin mRNA expression decreased in EPAC1/2 KO cells when compared to control. Activation of RhoA, cdc42, Rac1 and FAK were observed in an EPAC1/2 dependent manner and there was diminished cytoskeletal assembly in EPAC1/2 KO cells.

Conclusion EPAC1/2 are critical signaling intermediates in osteoclast differentiation that permit RANKL-stimulated NFkB nuclear translocation and actin rearrangements. Targeting this signaling intermediate may diminish bone destruction in inflammatory arthritis.


Disclosure:

A. Mediero,
None;

M. Perez-Aso,
None;

B. N. Cronstein,

Canfite Pharma,

1,

AstraZeneca,

2,

Cellgene,

2,

Gilead,

2,

NIH,

2,

NYU School of Medicine,

3,

Bristol-Myers Squibb,

5,

Pfizer Inc,

5,

Eli Lilly and Company,

5,

Rheumatology Reseach Foundation,

6,

ACR,

6,

Arthritis Foundation,

6.

  • Tweet
  • Email
  • Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/activation-of-epac12-is-essential-for-osteoclast-formation-by-modulating-nfkb-nuclear-translocation-and-actin-cytoskeleton-rearrangements/

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