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

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 () and Lianping Xing ()
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Wen Sun: University of Rochester Medical Center
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
Jennifer H. Anolik: University of Rochester Medical Center
Lianping Xing: University of Rochester Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07626-8

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