The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation of human osteoclastic bone resorption in vitro.

Prostaglandins increase human osteoclast generation in vivo whereas they have been shown to exert the opposite effect in vitro: the latter results are based on enumeration of osteoclast-like cells, whose nature is controversial. We have generated human osteoclasts in vitro as assessed by bone resorption, a function unique to the osteoclast, and analysed the role of prostaglandin E2 (PGE2) in osteoclast activity. Human bone marrow cells were cultured to form a mature stroma and then sedimented onto bone slices with or without a recharge of non-adherent bone marrow cells. Bone resorption was increased by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and PGE2 and inhibited by indomethacin: this inhibition was reversed by addition of PGE2. Our work supports the observation that PGE2 increases bone resorption in vivo and demonstrates the value of assessing osteoclast generation and activity in vitro using bone resorption.