IL-1α Stimulates the Formation of Osteoclast-like Cells via RANK-RANKL Signaling System by Osteoblasts and Monocytes

Abstract

We examined the effect of the inflammatory mediator interleukin-1α (IL-1α) on the expression of macrophage colony-stimulating factor (M-CSF), osteoprotegerin (OPG), and prostaglandin E₂ (PGE₂) in rat osteoblasts, and the indirect effect of IL-1α on the formation of osteoclast-like cells. The expression of M-CSF and OPG were estimated by determining protein levels using Western blot analysis. PGE₂ expression was determined using ELISA. The formation of osteoclast-like cells was estimated using tartrate-resistant acid phosphatase (TRAP) staining of osteoclast precursors in culture with conditioned medium from IL-1α-treated osteoblasts and the soluble receptor activator of NF-κB ligand (RANKL). M-CSF and PGE₂ expression in osteoblasts increased markedly in cells cultured with IL-1α, whereas OPG expression decreased. The conditioned medium containing M-CSF and PGE₂ produced by IL-1α-treated osteoblasts and soluble RANKL increased the TRAP staining of osteoclast precursors. These results suggest that IL-1α stimulated the formation of osteoclast-like cells via an increase in M-CSF and PGE₂ production, and a decrease in OPG production by osteoblasts.