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Cited 24 time in webofscience Cited 25 time in scopus
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Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts

Authors
Hyun, Jong JinChun, Hoon JaiKeum, BoraSeo, Yeon SeokKim, Yong SikJeen, Yoon TaeLee, Hong SikUm, Soon HoKim, Chang DuckRyu, Ho SangKim, Sin GonJung, Woon-Won
Issue Date
Dec-2010
Publisher
SPANDIDOS PUBL LTD
Keywords
proton pump inhibitor; omeprazole; osteoclast; osteoblast
Citation
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.26, no.6, pp.877 - 883
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume
26
Number
6
Start Page
877
End Page
883
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/14283
DOI
10.3892/ijmm_00000537
ISSN
1107-3756
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-kappa B 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 osteocalein 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.
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2. Clinical Science > Department of Endocrinology and Metabolism > 1. Journal Articles
2. Clinical Science > Department of Internal Medicine > 1. Journal Articles
5. Others > Others(Medicine) > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

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Seo, Yeon Seok
Anam Hospital (Department of Gastroenterology and Hepatology, Anam Hospital)
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