ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2820

Dual Role for B Cells in Promoting Bone Erosion in Rheumatoid Arthritis Via Effects on Osteoclast and Osteoblast Differentiation

Nida Meednu1, Hengwei Zhang2, Teresa Owen3, Lianping Xing4 and Jennifer H. Anolik5, 1Allergy, Immunology and Rheumatology, University of Rochester, Rochester, NY, 2Pathology and Laboratory Medicine, University of Rochester, Rochester, NY, 3Rheumatology, University of Rochester, Rochester, NY, 4Pathology & Lab Medicine, University of Rochester, Rochester, NY, 5Medicine- Allergy, Immunology and Rheumatology, University of Rochester, Rochester, NY

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: B cells, Osteoblasts, osteoclasts and rheumatoid arthritis (RA)

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis I: Mechanisms of Joint Damage

Session Type: Abstract Submissions (ACR)

Background/Purpose

Rheumatoid arthritis (RA) is a systemic autoimmune disease that often leads to joint damage, a process mediated by an imbalance between bone resorption and bone formation. Additional evidence implicates the role of B cells in joint destruction including the presence of B cell aggregates in RA synovium and subchondral bone and the efficacy of B cell depletion therapy in halting radiographic progression. However, B cell effects on bone have been described as mediated via indirect influences on other immune cell such as T cells. Whether B cells directly affect bone homeostasis in RA is not known. In this study we investigated the effects of B cells on osteoclast (OC) and osteoblast (OB) functions in RA. 

Methods

Isolated B cells from peripheral blood of healthy controls (HC) or RA patients were stimulated with α-CD40 and PMA for 96 h, and RANKL and TNF production was assessed by flow cytometry, ELISA, and qPCR. Stimulated and un-stimulated B cells were fixed then co-cultured with CD14+ monocytes isolated from HC along with M-CSF and sub-optimal levels of exogenous RANKL (10ng/ml). OC formation in vitrowas examined by TRAP staining. For OB differentiation assays, stimulated and un-stimulated B cells were co-cultured in Transwells with human mesenchymal stem cells (hMSCs) (Lonza, #PT-2501) for 24 h and the expression of OB transcription factor RUNX2 and Notch signaling molecules, Hes1 and Hey1 in hMSCs was detected by qPCR.

Results

HC B cells stimulated with α -CD40 and PMA produce significant amounts of RANKL as compare to un-stimulated B cells (%RANKL+: 4.9±0.94 vs. 0.413±0.095, P<0.0001).  Stimulated HC B cells promoted more OC formation than that of un-stimulated B cells (#OC/well: 66±8 vs. 4±1, P< 0.0001), which can be blocked by RANKL neutralizing antibody (#OC/well: 66±8 vs. 21±3, P<0.0001). Notably, stimulated RA B cells induced significantly more OC formation in comparison to HC B cells (using the same donor for OCP) (#OC/well: RA: 60±7 vs. HC: 12±7, P<0.001). In parallel, RA memory B cells expressed higher RANKL than memory B cells from HC (%RANKL+: 20.4±1.68 vs. 11.25±3.15, P<0.05). In addition to RANKL, stimulated B cells produce TNFα (91±11.6 pg/ml, n=4) a cytokine that we reported recently to inhibit OB differentiation of murine CD45- MSCs via up-regulating the Notch signaling pathway. In co-culture with hMSCs, stimulated RA B cells significantly reduced RUNX2 expression in hMSCs as compared to un-stimulated B cells  (Runx2/actin: 0.21±0.01vs. 1±0.04 P=0.002, n=3), which was associated with increased levels of Hes1 and Hey1. In agreement with this finding, RA CD45- cells (MSC-enriched cells) isolated from peripheral blood have reduced expression of RUNX2 and increased expression of Hes1 and Hey1 compared to HC (n=11 for RA, n=14 for HC), suggesting abnormal OB function in vivo. 

Conclusion

Our finding suggest that B cells play a critical role in promoting bone erosion in RA both by directly enhancing osteoclastogenesis and inhibiting osteoblast differentiation.


Disclosure:

N. Meednu,
None;

H. Zhang,
None;

T. Owen,
None;

L. Xing,
None;

J. H. Anolik,
None.

  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/dual-role-for-b-cells-in-promoting-bone-erosion-in-rheumatoid-arthritis-via-effects-on-osteoclast-and-osteoblast-differentiation/

Advanced Search

Your Favorites

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

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.