title: Infliximab acts directly on human osteoclast precursors and enhances osteoclast formation induced by receptor activator of nuclear factor kappaB ligand in vitro.
abstract: Infliximab is known to protect against the development of joint destruction. In the present study, we sought to determine whether Infliximab acts directly on human osteoclast precursors and influences monocyte-osteoclast differentiation induced by receptor activator of nuclear factor kappaB ligand (RANKL) in vitro. Peripheral blood mononuclear cells (PBMCs) isolated from rheumatoid arthritis (RA) patients and normal controls were cultured in the presence of RANKL and macrophage colony stimulating factor. Infliximab, antihuman tumor necrosis factor alpha (TNFalpha), antihuman TNF soluble receptor p55 (TNFR p55), and antihuman TNF soluble receptor p75 (TNFR p75) antibodies were added. Osteoclast formation was determined by assessing the number of tartrate-resistant acid phosphatase (TRAP) staining cells and the extent of lacunar resorption. Addition of Infliximab resulted in a marked increase in the number of TRAP-positive multinucleated cells (TRAP(+) MNCs) and in the extent of lacunar resorption compared with the control cultures. Antihuman TNFalpha antibody showed the same effect; however, the addition of neither TNFR p55 nor TNFR p75 antibody affected the extent of TRAP(+) MNCs and lacunar resorption. Our results suggest that infliximab acts directly on early osteoclast precursors, and stimulates osteoclast formation and lacunar resorption induced by RANKL in vitro.
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita-gun, Oita, 879-5593, Japan.
authors.forename: Chikahiro
authors.initials: C
authors.lastname: Takita
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujikawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Itonaga
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Taira
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kawashima
authors.forename: Takehiko
authors.initials: T
authors.lastname: Torisu