Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts

Jong Jin Hyun, Hoon Jai Chun, Bora Keum, Yeon Seok Seo, Yong Sik Kim, Yoon Tae Jeen, Hong Sik Lee, Soon Ho Um, Chang Duck Kim, Ho Sang Ryu, Sin Gon Kim, Woon Won Jung

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18 Citations (Scopus)

Abstract

The use of proton pump inhibitors (PPIs) seems to be related to increased fracture risk but the mechanism is unclear. In an effort to clarify the mechanism, we evaluated the effect of omeprazole, a representative of the PPIs, on the expression of transcription factors in osteoclasts and osteoblasts. Murine RAW264.7 and MC3T3-E1 cells were used for osteoclast and osteoblast analysis, to which various concentrations of omeprazole were added. RAW264.7 cells with ?3 nuclei were considered tartrate-resistant acid phosphatase (TRAP)-positive, i.e. activated osteoclasts. Expressions of the calcitonin receptor (CTR), c-fos, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and matrix metalloproteinase (MMP)-9 mRNA in osteoclasts were evaluated. Gene expression of osteocalcin and of the osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) ratio in osteoblasts was examined and Western blotting of NFATc1 was performed. Treating the osteoclasts with increasing doses of omeprazole did not affect TRAP positivity, but significantly decreased the expressions of CTR, c-fos, NFATc1, and MMP-9 regardless of the omeprazole concentration. The expression of osteocalcin and of the OPG/RANKL ratio in osteoblasts was augmented with increasing omeprazole concentrations. The result of the Western blot analysis with NFATc1 was similar to that of the expression of NFATc1 mRNA. Omeprazole decreased the activation of osteoclasts but increased that of osteoblasts in vitro, in part causing an osteopetrosis-like effect. Together with the effect of omeprazole on calcium homeostasis, increased fracture risk may be due to the osteopetrorickets-like effect of omeprazole.

Original languageEnglish
Pages (from-to)877-883
Number of pages7
JournalInternational journal of molecular medicine
Volume26
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • Omeprazole
  • Osteoblast
  • Osteoclast
  • Proton pump inhibitor

ASJC Scopus subject areas

  • Genetics

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    Hyun, J. J., Chun, H. J., Keum, B., Seo, Y. S., Kim, Y. S., Jeen, Y. T., Lee, H. S., Um, S. H., Kim, C. D., Ryu, H. S., Kim, S. G., & Jung, W. W. (2010). Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts. International journal of molecular medicine, 26(6), 877-883. https://doi.org/10.3892/ijmm-00000537