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Differential effects of fluoride during initiation and progression of mineralization of osteoid nodules formed in vitro
Author(s) -
Bellows C.G.,
Aubin J.E.,
Heersche J.N.M.
Publication year - 1993
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.5650081110
Subject(s) - osteoid , mineralization (soil science) , alkaline phosphatase , chemistry , medicine , in vitro , phosphate , endocrinology , fluoride , biochemistry , biology , enzyme , inorganic chemistry , organic chemistry , nitrogen
Osteoid nodules form in cultures of fetal rat calvarial (RC) cells grown in medium containing 10% FBS and 50 μg/ml of ascorbic acid. When 10 mM β‐glycerophosphate (β‐GP) is added, osteoid nodules mineralize in two phases: an initiation phase, which is dependent upon alkaline phosphatase activity for conversion of β‐GP to P i , and a progression phase that proceeds independently of alkaline phosphatase activity and does not require exogenous phosphate. We have now used this system to investigate the effects of fluoride (F − ) on mineralization. In cultures in which osteoid was formed and mineralization initiated in the presence of F − , a dose‐dependent inhibition of the initiation of mineralization occurred over a concentration range of 25–500 μM F − ( p < 0.001 in all cases). The initiation of mineralization was not inhibited if F − was removed from the cultures at the time when mineralization was initiated with β‐GP. In osteoid nodules grown in the absence of F − , addition of F − resulted in a dose‐dependent inhibition of the initiation of mineralization, with significant decreases in 45 Ca uptake occurring at F − concentrations of 3 μM ( p < 0.01) and higher. However, if F − was added to cultures after mineralization was initiated in the absence of F − , a stimulation of 45 Ca uptake was observed at F − concentrations of 250 μM and above ( p < 0.001). F − (1–1000 μM) did not affect the conversion of β‐GP to P i or alkaline phosphatase activity in the cultures. The data show that mineralization of osteoid formed in the presence of F − is unaffected when F − is removed before initiation, that F − inhibits the initiation phase of mineralization at concentrations as low as 3 μM, and that F − stimulates mineralization during the progression phase. These data agree with clinical observations of hypermineralization of existing bone and hypomineralization of newly formed osteoid in association with F − administration.