Similarities and differences between the effects of ipriflavone and vitamin K on bone resorption and formation in vitro.
The effects of ipriflavone and vitamin K on bone metabolism were examined using a culture system. Vitamin K1 and vitamin K2 (10(-7)M-10(-5)M) inhibited both the activation of mature osteoclasts and the formation of new osteoclasts without affecting the growth of progenitor cells in cultures of mouse unfractionated bone cells. The inhibitory effects of vitamin K on bone resorption were similar to those of ipriflavone and were not affected by the vitamin K antagonist warfarin. When ipriflavone was added to the culture medium in combination with vitamin K2, an additive inhibitory effect on bone resorption was observed. An additive effect was also observed in organ cultures of mouse calvaria. On the other hand, ipriflavone, but neither vitamin K1 nor vitamin K2, stimulated cellular alkaline phosphatase (ALP) activity on rat bone marrow stromal cells under culture conditions in which cells subsequently form mineralized bone-like tissue. Vitamin K1 and vitamin K2 also did not modulate the stimulatory effect of ipriflavone on the ALP activity of the cells. These results suggest that the inhibitory effects of vitamin K on bone resorption are similar to those of ipriflavone through mechanisms that may be independent of the gamma-carboxylation system, while the effects of vitamin K on osteoblast phenotype expression are different from those of ipriflavone.
Notoya
K
K
Department III, Takeda Chemical Industries Ltd., Osaka, Japan.
Yoshida
K
K
Shirakawa
Y
Y
Taketomi
S
S
Tsuda
M
M
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology; D001862:Bone Resorption / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002458:Cell Fractionation; D002478:Cells, Cultured; D004357:Drug Synergism; D005269:Femur / Q000166:cytology; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D010641:Phenotype; D051381:Rats; D013234:Stem Cells / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D014812:Vitamin K / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014859:Warfarin / Q000494:pharmacology
D007529:Isoflavones; D014812:Vitamin K; D014859:Warfarin; C018986:ipriflavone; D000135:Acid Phosphatase