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Lithium inhibits calcitriol‐stimulated formation of multinucleated cells in human long‐term marrow cultures
Author(s) -
Pepersack Thierry,
Corazza Francis,
Demulder Anne,
Guns Martine,
Fondu Pierre,
Bergmann Pierre
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090509
Subject(s) - bone resorption , endocrinology , osteoclast , medicine , multinucleate , parathyroid hormone , calcitriol , tartrate resistant acid phosphatase , resorption , acid phosphatase , bone marrow , chemistry , cell culture , lithium (medication) , microbiology and biotechnology , biology , calcium , vitamin d and neurology , biochemistry , enzyme , receptor , genetics
We observed that lithium (3 mM) blocked the 1,25‐dihydroxyvitamin D [1,25‐(OH) 2 D 3 ]‐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)D 3 ‐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) 2 D 3 ‐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) 2 D 3 , 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) 2 D 3 , (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) 2 D 3 . When Li was added to the cells the first week of culture only, we observed the full inhibitory effect; conversely, if Li was added for the last week of culture only, no inhibitory effect was seen. These data show that Li interferes with the recruitment of osteoclast‐like cells from their precursors, probably at an early stage of differentiation.