Vitamin K2 and geranylgeraniol, its side chain component, inhibited osteoclast formation in a different manner.
We comparatively examined the mechanism by which vitamin K(2) (Menatetrenone, MK4) and its side chain component, geranylgeraniol (GGO), inhibited osteoclast formation in the co-culture system of stromal cells with spleen cells. Both MK4 and GGO inhibited osteoclast formation induced by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)). MK4, but not GGO, inhibited cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in the co-culture system. To elucidate the precise mechanism of the inhibitory effect of GGO on osteoclast formation, the co-cultured cells were stimulated with PGE(2). GGO, but not MK4, inhibited osteoclast formation via suppression of the receptor activator of NF-kappaB ligand (RANKL) expression. Moreover, GGO abolished the disruption of osteoclastic actin rings induced by nitrogen-containing bisphosphonate (N-BP), whereas MK4 did not affect it at all. These data suggest that MK4 inhibited osteoclast formation independently of GGO, and that MK4, but not GGO, has no competitive action on the anti-osteoporotic effect of N-BP.
Hiruma
Yuko
Y
Department of Cellular Physiological Chemistry, Graduated School, Tokyo Medical and Dental University 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
Nakahama
Ken-ichi
K
Fujita
Hiroshi
H
Morita
Ikuo
I
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D004164:Diphosphonates / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D021122:Protein Subunits; D013154:Spleen / Q000187:drug effects / Q000502:physiology; D024482:Vitamin K 2 / Q000737:chemistry / Q000494:pharmacology*
D004164:Diphosphonates; D004224:Diterpenes; D007527:Isoenzymes; D021122:Protein Subunits; D024482:Vitamin K 2; C017338:geranylgeraniol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone