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Bone‐ and Cartilage‐Protective Effects of a Monoclonal Antibody Against Colony‐Stimulating Factor 1 Receptor in Experimental Arthritis
Author(s) -
Toh MyewLing,
Bonnefoy JeanYves,
Accart Nathalie,
Cochin Sandrine,
Pohle Sandy,
Haegel Hélène,
Meyer Micael,
Zemmour Christophe,
Preville Xavier,
Guillen Christine,
Thioudellet Christine,
Ancian Philippe,
Lux Anja,
Sehnert Bettina,
Nimmerjahn Falk,
Voll Reinhard E.,
Schett Georg
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38624
Subject(s) - medicine , arthritis , cartilage , inflammation , osteoclast , immunology , rheumatoid arthritis , synovial fluid , monocyte , osteoarthritis , endocrinology , receptor , pathology , anatomy , alternative medicine
Objective Colony‐stimulating factor 1 receptor (CSF‐1R) essentially modulates monocyte proliferation, migration, and activation, which are considered important for the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine CSF‐1R expression in human RA as well as the efficacy of a specific anti–CSF‐1R monoclonal antibody (AFS98) in 2 different animal models of RA. Methods CSF‐1R expression was examined in blood, synovium, and bone samples from RA patients, osteoarthritis (OA) patients, and healthy subjects. The efficacy of AFS98 was examined by clinical assessment, histology, and bone histomorphometry in collagen‐induced arthritis (CIA) and serum‐transfer arthritis. Results CSF‐1R expression was increased in the synovium of RA patients compared to OA patients and healthy controls in fibroblast‐like synoviocytes, follicular dendritic cells, macrophages, and osteoclasts. Circulating RA monocytes and neutrophils but not lymphocytes were CSF‐1R+. In mice, blockade of CSF‐1R abrogated cartilage damage, bone erosion, and systemic bone loss, and this was associated with the depletion of osteoclasts in both models. While blockade of CSF‐1R did not affect inflammation in passive serum‐transfer arthritis, it significantly reduced inflammation in CIA, and this was associated with the absence of synovial macrophages and reduced splenic CD11b+Gr‐1− monocytes. Conclusion CSF‐1R was broadly expressed in human RA. Blockade of CSF‐1R protected against bone and cartilage destruction in both mouse models and also showed significant antiinflammatory effects in the CIA model. These data provide evidence for CSF‐1R as a therapeutic target in RA.