Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts

Abstract

Osteopontin is a matrix protein which belongs to the integrin superfamily and is involved in cell adhesion. In the present study, we examined the regulation of the mRNA expression of osteopontin by interleukin 1α (IL-1α) in osteoblasts. IL-1α greatly increased the steady-state level of osteopontin mRNA in both a mouse osteoblastic cell line (MC3T3-E1) and mouse primary osteoblast-like cells. The increase in the osteopontin mRNA expression by IL-1α was dose-dependent at a range of 0.004−0.2 nM. This was most likely due to an increase in the transcriptional rate, not to an increase in the stability of osteopontin mRNA. The in vitro nuclear transcription experiment showed that IL-1α-treated MC3T3-E1 cells increased the synthesis of osteopontin mRNA. Besides IL-1α, tumor necrosis factor α (TNF-α), lipopoly-saccharides (LPS) and 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃) increased the osteopontin mRNA expression in both the clonal osteoblasts (MC3T3-E1) and the primary osteoblast-like cells. In response to such bone-resorbing agents, primary osteoblast-like cells expressed osteopontin mRNA much more strongly than primary fibroblast-like cells isolated from mouse calvaria. Both IL-1α and α,25(OH)₂D₃ greatly increased the production of 68 and 62 kDa phosphoproteins in conditioned media of MC3T3-E1 cell cultures, which probably correspond to osteopontin. These results suggest that osteopontin plays an important role in bone remodeling, in particular bone resorption.