Current topics in pharmacological research on bone metabolism: inhibitory effects of bisphosphonates on the differentiation and activity of osteoclasts.
Despite the extensive use of bisphosphonates (BPs) in the treatment of metabolic bone diseases associated with increased osteoclastic bone resorption, the precise mechanism of their action on bone metabolism is still unclear. To clarify at which stages of osteoclast differentiation and activation that BPs influence, we examined the osteoclasts generated from mononuclear precursors and osteoclasts in the calvaria by laser scanning confocal microscopy. The studies showed that BPs inhibit lipopolysaccharide- or parathyroid hormone-induced osteoclast differentiation, fusion, attachment, actin ring formation, and activation and that both beta3 integrin and osteopontin have an important role in cytoskeletal rearrangements associated with cell attachment and resorption in osteoclasts.
Suzuki
Keiko
K
Department of Pharmacology, School of Dentistry, Showa University, Japan. suzukik@dent.showa-u.ac.jp
Takeyama
Sadaaki
S
Sakai
Yasushi
Y
Yamada
Shoji
S
Shinoda
Hisashi
H
D000199:Actins / Q000378:metabolism; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D039302:Integrin alphaVbeta3; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin