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Aluminum potentiates the effect of fluoride on tyrosine phosphorylation and osteoblast replication in vitro and bone mass in vivo
Author(s) -
Caverzasio Joseph,
Imai Toshio,
Ammann Patrick,
Burgener Dominique,
Bonjour JeanPhilippe
Publication year - 1996
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.5650110108
Subject(s) - osteoblast , in vivo , endocrinology , chemistry , medicine , phosphorylation , protein kinase c , kinase , in vitro , tyrosine phosphorylation , tyrosine kinase , protein kinase a , signal transduction , biology , biochemistry , microbiology and biotechnology
Osteosclerosis in workers exposed to fluoride (F) and aluminum (Al) (industrial fluorosis) led to the use of F as a treatment to increase bone mass in osteoporosis patients. Because the influence of traces of Al on the effects of F on bone formation is heretofore unknown, we have investigated this issue both in vitro and in vivo. We have found that minute amounts of Al (≤10 −5 M) potentiate the effects of F in vitro such that osteoblast proliferation increased by 15 ± 2.7% at 50 μM ( p < 0.001) and by 117.6 ± 5.1% at 750 μM ( p < 0.001), concentrations of F with no mitogenic effect alone. F + Al time‐dependently modulated a growth factor signaling pathway(s) associated with enhanced tyrosine phosphorylation (TyrP) of several proteins (p90 [2.9x], p77 [4.9x], p68 [9.6x], and mitogen activated protein kinases [3x]). TyrP was only slightly or not at all changed by F and Al alone, respectively. The effects of F + Al on TyrP and cell proliferation were markedly reduced by 100 μM ryrphostin‐51, a tyrosine kinase inhibitor. Protein kinase A (PKA) and protein kinase C (PKC) pathways were not involved in this response. In vivo, F + Al administered for 8 months, at doses that had no effect when the minerals were administered individually, significantly enhanced proximal tibia bone mineral density (BMD) by 6.3 ± 1% compared with initial values and by 2‐fold compared with control ovariectomized rats ( p < 0.0001). These effects are consistent with a crucial role of Al in osteosclerosis observed in industrial fluorosis. The results suggest that the combination of F + Al modulates a growth factor‐dependent TyrP pathway enhancing mitogen‐activated protein kinase and osteoblastic proliferation and bone mass.