Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 32, Issue 8, Pages 1681-1691Publisher
WILEY
DOI: 10.1002/jbmr.3158
Keywords
PERIARTICULAR BONE LOSS; RHEUMATOID ARTHRITIS; OSTEOCLASTS; AUTOANTIBODIES; CITRULLINATED PROTEINS
Categories
Funding
- Swedish Research Council [537-2013-7370]
- Deutsche Forschungsgemeinschaft (SPP1468 Immunobone)
- Deutsche Forschungsgemeinschaft [CRC 1181]
- Bundesministerium fur Bildung und Forschung (BMBF)
- Marie-Curie project Osteoimmune
- TEAM project of the European Union
- IMI
- Swedish Association for Medical Research
- Interdisciplinary Centre for Clinical Research of the University of Erlangen-Nuremberg
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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 peptidylarginine 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-alpha, 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. (C) 2017 American Society for Bone and Mineral Research.
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