Interleukin-1 α produced in human gingival fibroblasts stimulates the survival and fusion of osteoclasts via cell-to-cell contact

Abstract

We here investigated effects of intracellular Interleukin-1α (IL-1 α) produced in human gingival fibroblasts (HGF) on differentiation of osteoclasts (OCLs) precursor cells into OCLs and survival and fusion of mononuclear OCLs. Treatment with IL-1 β stimulated to produce intracellular IL-1 αin HGF. The cell layer of HGF treated with IL-1 β or not was subsequently fixed with 1 % paraformaldehyde. Cell membrane of the fixed HGF treated with IL-1 β possessed IL-1 activity, which was mainly attributed to IL-1 α. Soluble form of receptor activator of NF-κB ligand/ osteocalasts differentiation factor (RANKL/ODF) stimulated differentiation of RAW cells, a OCLs precursor cell line, into tartelet resistant acid phosphatase (TRAP) -positive OCLs. However, the RAW cells could not be differentiated into the TRAP-positive OCLs, when the cells were cultured on the fixed HGF treated with IL-1 β. On the other hand, the fixed HGF treated with IL-1 β stimulated survival and fusion of TRAP-positive mononuclear OCLs, when prefusion OCLs (pOCs), which were formed in coculture of murine osteoblasts and bone marrow cells, were cultured on the fixed HGF. The stimulatory effects of the fixed HGF treated with IL-1 β was suppressed by adding anti-human IL-1 α antibody or inhibition of cell-to-cell contact between the pOCs and the fixed HGF, but addition of anti-human M-CSF antibody and osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) had no effect. These results suggest that intracellular IL-1 α produced in HGF treated with IL-1 β has no effect on differentiation of OCLs precursor cells into OCLs, however it stimulates survival and fusion of mononuclear OCLs via cell-to-cell contact.