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Dose‐dependent inhibitory effects of proton pump inhibitors on human osteoclastic and osteoblastic cell activity
Author(s) -
CostaRodrigues João,
Reis Sara,
Teixeira Sónia,
Lopes Sandra,
Fernandes Maria H.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12478
Subject(s) - osteoblast , chemistry , osteoclast , intracellular , lansoprazole , bone resorption , apoptosis , microbiology and biotechnology , signal transduction , mesenchymal stem cell , cell growth , bone remodeling , bone cell , endocrinology , omeprazole , pharmacology , medicine , in vitro , biochemistry , biology
Proton pump inhibitors ( PPI s), a class of molecules that are used to decrease gastric acid production, might have adverse effects on bone metabolism. The aim of this study was to characterize the concentration‐dependent and time‐dependent effects of three PPI s (omeprazole, esomeprazole, and lansoprazole) on human osteoclast precursor cells isolated from peripheral blood, and on human mesenchymal stem cells (osteoblast precursors). Cell cultures were characterized for total protein content, apoptosis, and several osteoclastic/osteoblastic features, and also for the involvement of some intracellular signaling pathways. PPI s caused a dose‐dependent decrease in cellular density, which correlated with an increase in the apoptosis rate, effects that became statistically significant at concentrations ≥ 10 −5 m . They also inhibited phenotype‐related gene expression and functional parameters. For both cell types, cellular function, i.e. osteoclastic resorption and the formation of mineralized deposits by osteoblastic cells, was more affected than proliferation‐related parameters. The three PPI s showed similar qualitative and quantitative effects, but displayed some differences in the underlying intracellular signaling pathways. These results suggest that PPI s might have a direct deleterious effect on bone cells, with the possibility of decreased bone turnover.