Lithium inhibits calcitriol-stimulated formation of multinucleated cells in human long-term marrow cultures.
We observed that lithium (3 mM) blocked the 1,25-dihydroxyvitamin D [1,25-(OH)2D3]-stimulated bone resorption in fetal rat long bones in culture. Because this inhibitory effect was not seen when bone resorption was stimulated by parathyroid hormone or interleukin-1, we reasoned that Li specifically inhibited events involved in the 1,25-(OH)D3-stimulated bone resorption. The increased bone resorption induced by vitamin D in culture is associated with differentiation and/or fusion of osteoclast progenitors. In the present work, we studied the effect of Li on the basal and 1,25-(OH)2D3-stimulated generation of multinucleated osteoclast-like cells (MNC) and MNC containing tartrate-resistant acid phosphatase (TRAP+) in long-term human bone marrow cultures. Total MNC and TRAP+ cells were counted after 3 weeks of culture. In the absence of both lithium and 1,25-(OH)2D3, total MNC and TRAP+ cell numbers were 146 +/- 22 and 110 +/- 18 per well, respectively (mean +/- SEM); in the presence of Li, corresponding figures were 79 +/- 17 and 59 +/- 14. When the generation of MNC and TRAP+ cells was stimulated with 1,25-(OH)2D3, (10(-8) M), total MNC and TRAP+ cells were 521 +/- 66 and 473 +/- 63, respectively, in the absence of Li and 251 +/- 44 and 155 +/- 27 in the presence of Li (p < 0.05). The inhibitory effect of Li was dose dependent and was not observed when the cultures were exposed to parathyroid hormone instead of 1,25-(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)
Pepersack
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Laboratory de Médecine Expérimentale, Hôpital Universitaire Brugmann, Université Libre de Bruxelles, Belgium.
Corazza
F
F
Demulder
A
A
Guns
M
M
Fondu
P
P
Bergmann
P
P
D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*
D008094:Lithium; D002117:Calcitriol