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Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis
Noriko Komatsu, … , Tomoki Nakashima, Hiroshi Takayanagi
Noriko Komatsu, … , Tomoki Nakashima, Hiroshi Takayanagi
Published March 15, 2021
Citation Information: J Clin Invest. 2021;131(6):e143060. https://doi.org/10.1172/JCI143060.
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Concise Communication Autoimmunity Bone Biology

Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis

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Abstract

In rheumatoid arthritis (RA), osteoclastic bone resorption causes structural joint damage as well as periarticular and systemic bone loss. Periarticular bone loss is one of the earliest indices of RA, often preceding the onset of clinical symptoms via largely unknown mechanisms. Excessive osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL) expressed by synovial fibroblasts causes joint erosion, whereas the role of RANKL expressed by lymphocytes in various types of bone damage has yet to be elucidated. In the bone marrow of arthritic mice, we found an increase in the number of RANKL-expressing plasma cells, which displayed an ability to induce osteoclastogenesis in vitro. Genetic ablation of RANKL in B-lineage cells resulted in amelioration of periarticular bone loss, but not of articular erosion or systemic bone loss, in autoimmune arthritis. We also show conclusive evidence for the critical contribution of synovial fibroblast RANKL to joint erosion in collagen-induced arthritis on the arthritogenic DBA/1J background. This study highlights the importance of plasma-cell RANKL in periarticular bone loss in arthritis and provides mechanistic insight into the early manifestation of bone lesion induced by autoimmunity.

Authors

Noriko Komatsu, Stephanie Win, Minglu Yan, Nam Cong-Nhat Huynh, Shinichiro Sawa, Masayuki Tsukasaki, Asuka Terashima, Warunee Pluemsakunthai, George Kollias, Tomoki Nakashima, Hiroshi Takayanagi

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Figure 1

The number of RANKL-expressing plasma cells increases in the bone marrow under arthritic conditions.

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The number of RANKL-expressing plasma cells increases in the bone marrow...
RANKL-Cre ROSA26-YFP mice with CIA were analyzed 3 weeks after the secondary immunization. The bone marrow (BM) of the tibias and femurs (A–G) and inflamed synovium (H and I) were analyzed. (A) YFP expression in bone marrow cells. (B) The number of YFPmid (left) and YFPhi (right) cells (n = 5–7). (C) Tnfsf11 mRNA expression in YFP– and YFPhi cells analyzed by qPCR (n = 5). (D) FACS profile of YFPhi cells. (E) The frequency of YFPhi cells in B-lineage cells in the bone marrow under arthritic conditions (n = 7). (F) The number of YFPhi plasma cells in the bone marrow (n = 5–7). (G) Frequency of YFPhi cells in the bone marrow plasma cells (n = 5–7). (H) YFP and CD45 expression in the synovium. (I) CD45– cells were examined for the expression of CD31, CD146, podoplanin, and Thy1. Representative data of 3 independent experiments are shown (A, D, and I). All data are expressed as the mean ± SEM. *P < 0.05; **P < 0.01 by unpaired Student’s t test. NS, not significant.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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