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Alendronate Modulates Osteogenesis of Human Osteoblastic Cells In Vitro
Author(s) -
Masahiro Tsuchimoto,
Yoshiaki Azuma,
Osamu Higuchi,
Izuki Sugimoto,
Noriko Hirata,
Mamoru Kiyoki,
Ikuo Yamamoto
Publication year - 1994
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.66.25
Subject(s) - chemistry , osteocalcin , in vitro , mineralization (soil science) , bone resorption , endocrinology , medicine , in vivo , bone remodeling , diphosphonates , resorption , bisphosphonate , osteoporosis , biochemistry , alkaline phosphatase , biology , enzyme , microbiology and biotechnology , organic chemistry , nitrogen
The bisphosphonates, which are carbon-substituted pyrophosphates, have been studied extensively both in vivo and in vitro to elucidate their effects on bone tissues and cells. However, because these agents were shown to have a potent inhibitory effect on bone resorption, the majority of studies have focused on only this aspect of bone metabolism. There appears to be less information regarding the direct effect of bisphosphonates on bone formation, so thus we undertook experiments to investigate the effects of bisphosphonates, especially alendronate, on the mineralization and matrix protein synthesis of human osteoblastic cells in vitro. The data show that the bisphosphonates, alendronate, etidronate and pamidronate, suppressed 1,25-dihydroxycholecalciferol (1,25(OH)2D3)-stimulated mineralization of human osteoblastic cells at high concentrations, while relatively lower concentrations of alendronate and etidronate potentiated mineralization of the cells in the presence of 1,25(OH)2D3. The potentiation of mineralization with alendronate was accompanied by increased synthesis of bone matrix proteins, osteocalcin and collagen, and the mRNA of pro alpha(I) collagen. These findings show that in addition to their well-known effects on bone resorption, bisphosphonates have significant and direct effects on osteogenesis in osteoblasts in vitro. The actual mechanism remains to be further investigated.

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