Bone‐ and Cartilage‐Protective Effects of a Monoclonal Antibody Against Colony‐Stimulating Factor 1 Receptor in Experimental Arthritis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 66; no. 11; pp. 2989 - 3000
• Main Authors: Toh, Myew‐Ling, Bonnefoy, Jean‐Yves, 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
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2014
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Cartilage - drug effects; Cartilage - metabolism; Cartilage - pathology; Case-Control Studies; Dendritic Cells - metabolism; Dendritic Cells - pathology; Disease Models, Animal; Female; Humans; Macrophages - metabolism; Macrophages - pathology; Male; Mice; Mice, Inbred DBA; Middle Aged; Monocytes - metabolism; Monocytes - pathology; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteoclasts - metabolism; Osteoclasts - pathology; Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Receptor, Macrophage Colony-Stimulating Factor - drug effects; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Rheumatism; Rodents; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology
• DOI: 10.1002/art.38624
• ISSN: 2326-5191; 2326-5205

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.