Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol--effects of 22-oxacalcitriol on osteoclast-like cell formation and bone-resorbing activity.
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)
Kanatani
M
M
Department of Medicine, Kobe University School of Medicine, Japan.
Sugimoto
T
T
Kaji
H
H
Kano
J
J
Chihara
K
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D016588:Anticarcinogenic Agents; D014316:Tritium; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase; D002117:Calcitriol; C051883:maxacalcitol; D013936:Thymidine