title: Bone- and cartilage-protective effects of a monoclonal antibody against colony-stimulating factor 1 receptor in experimental arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Transgene SA, Lyon, France.
authors.forename: Myew-Ling
authors.initials: ML
authors.lastname: Toh
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bonnefoy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Accart
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cochin
authors.forename: Sandy
authors.initials: S
authors.lastname: Pohle
authors.forename: Hélène
authors.initials: H
authors.lastname: Haegel
authors.forename: Micael
authors.initials: M
authors.lastname: De Meyer
authors.forename: Christophe
authors.initials: C
authors.lastname: Zemmour
authors.forename: Xavier
authors.initials: X
authors.lastname: Preville
authors.forename: Christine
authors.initials: C
authors.lastname: Guillen
authors.forename: Christine
authors.initials: C
authors.lastname: Thioudellet
authors.forename: Philippe
authors.initials: P
authors.lastname: Ancian
authors.forename: Anja
authors.initials: A
authors.lastname: Lux
authors.forename: Bettina
authors.initials: B
authors.lastname: Sehnert
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D016186:Receptor, Macrophage Colony-Stimulating Factor