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

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 4

RANKL produced by B-lineage cells contributes to the periarticular bone loss in arthritis.

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RANKL produced by B-lineage cells contributes to the periarticular bone ...
(A and B) Association of periarticular bone loss with an increase in the bone marrow plasma cell number. Bone volume per tissue volume of the distal femur (A, left, n = 3–8) and lumbar spine (L5) (A, right, n = 3–8) and joint erosion of the calcaneus bone (B, n = 3–6) during the course of CIA. (C) Number of plasma cells in femur and tibia (left) and lumber spine (L1–L3, right) during the course of CIA. (D) Representative μCT images of the distal femur of arthritic mice. Scale bars: 1 mm. (E) Bone volume per tissue volume (left) and the trabecular bone number (right) of distal femurs of arthritic mice 3 weeks after the secondary immunization (n = 5–11). (F and G) Representative TRAP+ staining (F) and the numbers of TRAP+ multinucleated cells per bone surface (G) of the tibia of arthritic mice (n = 5–9). Scale bar: 100 μm. All data are expressed as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 by 1-way ANOVA with the Holm-Sidak multiple-comparison test (A–C) or 2-way ANOVA with the Holm-Sidak multiple-comparison test (E and G). NS, not significant.