Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin

Engdahl C, Bang H, Dietel K, Lang S, Harre U, Schett G (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Journal of Bone and Mineral Research American Society for Bone and Mineral Research

Book Volume: 32

Pages Range: 1681-1691

Journal Issue: 8

DOI: 10.1002/jbmr.3158

Abstract

Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as a modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis, as well as local expression of cytokines, osteoclast genes, and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL-1, IL-6, and TNF-?, as well as PAD2 and PAD4 enzymes in the periarticular bone marrow. Furthermore, also anti-MCV antibody challenge induced significant periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of patients with rheumatoid arthritis. © 2017 American Society for Bone and Mineral Research.

Authors with CRIS profile

Stefanie Lang Department of Medicine 3 – Rheumatology and Immunology Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

ORGENTEC Diagnostika GmbH DE Germany (DE)

How to cite

APA:

Engdahl, C., Bang, H., Dietel, K., Lang, S., Harre, U., & Schett, G. (2017). Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin. Journal of Bone and Mineral Research, 32(8), 1681-1691. https://doi.org/10.1002/jbmr.3158

MLA:

Engdahl, Cecilia, et al. "Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin." Journal of Bone and Mineral Research 32.8 (2017): 1681-1691.

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