Ribosome inactivating protein B-chain induces osteoclast differentiation from monocyte/macrophage lineage precursor cells.

Abstract

Human osteoclast formation from mononuclear phagocyte precursors involves interactions between lectins and their receptors. A type-2 ribosome inactivating protein consists of an A chain and a B chain. The glycosylated B chain binds specifically to galactose moieties of sugar molecules. In this study we showed that the recombinant ribosome inactivating protein B-chain (rRBC) could induce osteoclast formation from human monocytes and murine RAW264.7 macrophages. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays demonstrated that differentiation of osteoclast-like cells was induced in the presence of rRBC in a dose-dependent manner. The rRBC-induced osteoclast differentiation was independent of caspase activation and apoptosis induction activity; however, rRBC-induced osteoclastogenesis was dependent on activation of NF-κB, ERK1/2, and p38 MAP kinase. Thus, our data demonstrated that rRBC induced osteoclast differentiation through a non-apoptotic signaling pathway. In addition to triggering apoptosis, the rRBC also induced osteoclast differentiation. According to this study, a novel role is proposed for rRBC in regulating osteoclast differentiation and in osteoimmunology.