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B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation

Author

Listed:
  • Wen Sun

    (University of Rochester Medical Center
    Nanjing Medical University)

  • Nida Meednu

    (University of Rochester Medical Center)

  • Alexander Rosenberg

    (University of Rochester Medical Center)

  • Javier Rangel-Moreno

    (University of Rochester Medical Center)

  • Victor Wang

    (University of Rochester Medical Center)

  • Jason Glanzman

    (University of Rochester Medical Center)

  • Teresa Owen

    (University of Rochester Medical Center)

  • Xichao Zhou

    (University of Rochester Medical Center)

  • Hengwei Zhang

    (University of Rochester Medical Center)

  • Brendan F. Boyce

    (University of Rochester Medical Center
    University of Rochester Medical Center)

  • Jennifer H. Anolik

    (University of Rochester Medical Center
    University of Rochester Medical Center)

  • Lianping Xing

    (University of Rochester Medical Center
    University of Rochester Medical Center)

Abstract

The function of B cells in osteoblast (OB) dysfunction in rheumatoid arthritis (RA) has not been well-studied. Here we show that B cells are enriched in the subchondral and endosteal bone marrow (BM) areas adjacent to osteocalcin+ OBs in two murine RA models: collagen-induced arthritis and the TNF-transgenic mice. Subchondral BM B cells in RA mice express high levels of OB inhibitors, CCL3 and TNF, and inhibit OB differentiation by activating ERK and NF-κB signaling pathways. The inhibitory effect of RA B cells on OB differentiation is blocked by CCL3 and TNF neutralization, and deletion of CCL3 and TNF in RA B cells completely rescues OB function in vivo, while B cell depletion attenuates bone erosion and OB inhibition in RA mice. Lastly, B cells from RA patients express CCL3 and TNF and inhibit OB differentiation, with these effects ameliorated by CCL3 and TNF neutralization. Thus, B cells inhibit bone formation in RA by producing multiple OB inhibitors.

Suggested Citation

  • Wen Sun & Nida Meednu & Alexander Rosenberg & Javier Rangel-Moreno & Victor Wang & Jason Glanzman & Teresa Owen & Xichao Zhou & Hengwei Zhang & Brendan F. Boyce & Jennifer H. Anolik & Lianping Xing, 2018. "B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07626-8
    DOI: 10.1038/s41467-018-07626-8
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