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: 2730

Netrin1 Is a Critical Autocrine Factor For Osteoclast Differentiation

Aranzazu Mediero1, Bhama Ramkhelawon2, Kathryn Moore2, P. Edward Purdue3, Steven R. Goldring4 and Bruce N. Cronstein5, 1Medicine, Division of Translational Medicine, NYU School of Medicine, New York, NY, 2Leon H. Charney Division of Cardiology, Department of Medicine,, NYU School of Medicine, New York, NY, 3Research, Hospital for Special Surgery, New York, NY, 4Hospital for Special Surgery, New York, NY, 5Internal Medicine, NYU School of Medicine, Division of Rheumatology, New York, NY

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Joint arthroplasty, osteoclasts, prevention and treatment

  • 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 II: Osteoclast Biology and Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Netrins have been extensively studied for their role in axonal guidance during neural development. In addition, netrins are chemopulsants for a variety of non-neuronal cell types via binding to their receptors Unc5b and DCC. Although thought to suppress inflammation in several settings, netrin1, acting via Unc5b, inhibits macrophage migration directed by chemokines CCL2 and CCL19 to promote macrophage retention in and exacerbation of atherosclerotic plaque. We asked whether Netrin1 was expressed during osteoclast (OC) differentiation and whether it plays a role in OC differentiation.

Methods: DEXAscan and MicroCT analysis were performed on Netrin1 deficient mice (radiation chimeras) and wildtype (WT, radiation chimeras) littermates. OC differentiation was studied as M-CSF/RANKL-stimulated differentiation of murine bone marrow precursors to TRAP+/multinucleated cells, in the presence/absence of recombinant Netrin1 and Unc5b antibody. Netrin1, Unc5b and DCC expression were studied by RT-PCR and Western Blot in primary bone marrow-derived osteoclasts. Netrin1 immunostaining was performed in human tissue obtained following primary prosthesis implantation or after prosthesis revision.

Results:

During OC differentiation cell-associated Netrin1 and Unc5b (but not DCC) protein expression increased by 30±2% and 98±4% respectively (p<0.001,n=4) and Netrin1 secretion increased by 66±2% (p<0.001, n=4). Consistently, RANKL stimulates an increase in Netrin1 and Unc5b mRNA expression during OC differentiation (25±4 and 3±0.5 fold change respectively p<0.001, n=4). Moreover, in Netrin1-deficient marrow precursors OC differentiation was diminished by 65±2% as compared to control (p<0.001, n=6), an effect reversed by addition of recombinant netrin1 to cultures (121±5% increased, p<0.5, n=4). An antibody to the netrin1 receptor Unc5b reduces OC formation by 57±6% (p<0.001, n=6) whereas an antibody to DCC had no effect on OC formation (5±4% reduction, p=NS vs. control, n=6). Finally, DEXAscan and MicroCT analysis demonstrated an increase in bone mineral density (BMD), total volume (TV), bone volume (BV) and TV/BV in both cortical and trabecular bone in Netrin1 deficient mice when compared to WT (p<0.01 for all, n=5). Netrin1 immunostaining in human tissue biopsies reflect enhanced expression in tissue from implant revision when compared to primary implants.

Conclusion: The chemorepulsant Netrin1 is required for osteoclast differentiation and stimulates OC differentiation by an autocrine mechanism. This finding suggests that Netrin1 may be a novel target to reduce OC-mediated bone resorption and to prevent joint prosthesis loosening.


Disclosure:

A. Mediero,

Filed a patent on use of adenosine A2AR agonists to prevent prosthesis loosening (pending). ,

9;

B. Ramkhelawon,
None;

K. Moore,
None;

P. E. Purdue,
None;

S. R. Goldring,

Boehringer Ingelheim,

2,

Pfizer Inc, Bone Therapeutics, Fidia Pharma, Inc, Abbott Laboratories,

5;

B. N. Cronstein,

Canfite Pharma,

1,

NIH, Gilead, Takeda, AstraZeneca,

2,

NYU School of Medicine,

3,

Merck-SeronoBristol-Myers Squibb, Novartis, CanFite Biopharmaceuticals, Cypress Laboratories, Regeneron (Westat, DSMB), Endocyte, Protalex, Allos, Inc., Savient, Gismo Therapeutics, Antares Pharmaceutical, Medivector,

5,

Multiple patents on adenosine receptors and bone metabolism, pharmacology,

9.

  • 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/netrin1-is-a-critical-autocrine-factor-for-osteoclast-differentiation/

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