Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture.
Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10(-5)M induced contraction of the cells starting 7.5 h after its addition. Contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10(-4)M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10(-5)M alendronate moved actively after washing, but at 10(-4)M the motility locus was very narrow. At 10(-4)M, the actin ring in the cells began to break down, beginning 6h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10(-5)M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10(-5)M, which is an effective dose for bone resorption.
Koshihara
Y
Y
Department of Nutrition, Tokyo Metropolitan Institute of Gerontology, Japan.
Kodama
S
S
Ishibashi
H
H
Azuma
Y
Y
Ohta
T
T
Karube
S
S
D019386:Alendronate / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D019386:Alendronate