INTERLEUKIN-1 REGULATES THE EXPRESSION OF OSTEOPONTIN MESSENGER-RNA BY OSTEOBLASTS

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 1-alpha (IL-l-alpha) in osteoblasts. IL-1-alpha 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-l-alpha 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-l-alpha-treated MC3T3-E1 cells increased the synthesis of osteopontin mRNA. Besides IL-1-alpha, tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharides (LPS) and 1-alpha,25-dihydroxyvitamin D3 (1-alpha,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-1-alpha and 1-alpha,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.