Suda Tatsuo

Interleukin 1 regulates the expression of osteopontin mRNA 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-1 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-1 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-1 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.

Biological activities of 24-fluoro-1α,25-dihydroxyvitamin D-2 and its 24-epimer

Abstract Biological activities of two epimeric 24-fluorinated vitamin D-2 analogs, 24-fluoro-1α,25-dihydroxyvitamin D-2 [24-F-1,25-(OH) 2 D 2 ] and its 24-epimer [24-epi-24-F-1,25-(OH) 2 D 2 ], were studied and compared with 1α,25-dihydroxyvitamin D-3 [1,25-(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D-2 [1,25-(OH) 2 D 2 ]. 24-F-1,25-(OH) 2 D 2 was nearly as active as 1,25-(OH) 2 D 3 and 1,25-(OH) 2 D 2 both in regulating calcium metabolism in vivo including bone mineral mobilization and intestinal calcium transport and in inducing differentiation of HL-60 cells. While 24-epi-24-F-1,25-(OH) 2 D 2 showed distinct properties in these two types of the actions. Though the 24-epimer was nearly as potent as 1,25-(OH) 2 D 3 in inducing differentiation of HL-60 cells, it showed little activity in regulating calcium metabolism in vivo. The fluorine atom introduced at the 24-position of either 1,25-(OH) 2 D 2 or its 24-epimer had no potentiating effect. This is in sharp contrast with the cases of 24- and 26,27-multifluorinated analogs of active vitamin D-3.