IL-1α stimulates osteoclast formation by increasing M-CSF and decreasing OPG

Objectives: Interleukin-1α (IL-1α) is one of the most potent bone-resorbing factors involved in the bone loss associated with inflammation. We examined the effect of the inflammatory mediator 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. Methods: Osteoblasts were cultured in α-minimum essential medium containing 10% fetal bovine serum with or without 100 units/ml of IL-1α for up to 14 days. The gene and protein expression of M-CSF and OPG were estimated by determining mRNA levels using the real-time polymerase chain reaction and protein levels using Western blot analysis. PGE₂ expression was determined using an enzyme-linked immunosorbent assay. 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). Results: 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. Conclusion: 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.