22-Oxacalcitriol (OCT), a synthetic
vitamin D3 analog, can mimic the ability of
calcitriol to differentiate
leukemia and skin cells, to enhance the immune response and to suppress
parathyroid hormone secretion, but has much less calcemic activity than that of
calcitriol. The mechanism of this selective action remains not fully understood, and the actions of OCT on bone metabolism are little known. The present study was, therefore, designed to investigate the effects of OCT and
calcitriol on: the proliferation and functions of osteoblastic MC3T3-E1 cells; osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells as well as from unfractionated bone cells in the presence of stromal cells;
bone resorption; and the proliferation of MC3T3-E1 cells via monocytes.
22-Oxacalcitriol and
calcitriol inhibited [3H]
thymidine (TdR) incorporation,
alkaline phosphatase activity and
collagen synthesis of MC3T3-E1 cells to a similar degree. Both OCT (10(-10)-10(-8) mol/l) and
calcitriol significantly and similarly stimulated osteoclast-like cell formation from both hemopoietic blast cells and unfractionated bone cells.
22-Oxacalcitriol (10(-10) and 10(-8) mol/l) significantly stimulated
bone resorption, although to a slightly lesser degree than did
calcitriol. Human monocyte-
conditioned medium (CM) significantly stimulated TdR incorporation into MC3T3-E1 cells. On the other hand, CM obtained from monocytes treated with
calcitriol (10(-10)-10(-8) mol/l) significantly inhibited TdR incorporation in a dose-related fashion, whereas CM obtained from monocytes treated with OCT (10(-10)-10(-8) mol/l) significantly stimulated TdR incorporation in a dose-related fashion.(ABSTRACT TRUNCATED AT 250 WORDS)