ERK map kinase is required in 1,25(OH)₂D₃-induced differentiation in human osteoblasts

Expression of alkaline phosphatase(ALP)activity represents a key event during the differentiation processes of osteoblasts, and the level of ALP activity has been routinely Used as a relative measure of differentiation stages of osteoblasts. In human osteoblasts, we showed that vitamin D₃ analogue, 1,25(OH)₂D₃, had a stimulatory effect on ALP activity after 3 days, compared with control. The treatment of PD098059, an ERK MAP Kinase inhibitor, had a reducing effect on ALP activity, a differentiation marker in 1,25(OH)₂D₃-treated primary human osteoblasts. However, SB203580, a potent p38 MAP Kinase inhibitor, had no effect on the differentiation in this system. This indicates that ERK, not p38, is directly related to 1,25(OH)₂D₃-stimulated ALP activity in primary human osteoblasts. These results also show that the vitamin D₃ analogue stimulates ERK1 activation in primary human osteoblasts. This finding provides one of signaling pathways for differentiation in primary human osteoblasts.