Amelioration of bone loss in collagen-induced arthritis by neutralizing anti-RANKL monoclonal antibody.
Receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are pivotal regulators of osteoclast differentiation. RANK and RANKL also mediate T cell/dendritic cell (DC) interaction. Previous study has shown that RANK/RANKL interaction induces prolonged DC survival and antigen presentation. In the present study, we have newly established a hybridoma which produces neutralizing anti-RANKL monoclonal antibody (IK22-5). By treating collagen-induced arthritis (CIA) mice with IK22-5, we have investigated the role of RANKL in the pathogenesis of CIA. Although IK22-5 had no effect on immune responses or inflammation, it ameliorated bone loss at the site of inflammation. Histological analyses revealed that osteoclast formation was impaired at the site of joint inflammation in IK22-5-treated CIA mice. These results suggest the utility of anti-RANKL mAb for the prevention of osteoporosis associated with joint inflammation in RA.
Kamijo
Seiji
S
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. s-kamijo@med.juntendo.ac.jp
Nakajima
Atsuo
A
Ikeda
Kaori
K
Aoki
Kazuhiro
K
Ohya
Keiichi
K
Akiba
Hisaya
H
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001862:Bone Resorption / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000276:immunology*; D003094:Collagen; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D003094:Collagen