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The epithelial sodium channel is involved in dexamethasone-induced osteoblast differentiation and mineralization

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Abstract

Purpose

Glucocorticoids (GCs) can facilitate bone formation, but prolonged GCs exposure in vivo can lead to osteoporosis. The mechanisms underlying these reciprocal effects have not been elucidated.

Methods

The epithelial sodium channel (ENaC) is a possible regulator of osteoblast proliferation and differentiation, so we examined whether ENaC was involved in mediating the effects of dexamethasone (Dex) on osteoblast.

Result

Expression of the functional α-ENaC subunit was upregulated by 10−8M and 10−6M Dex, but decreased by 10−4M Dex. Furthermore, Dex had similar dose-dependent effects on the expression of three osteogenic genes, Cbfa1, OPN, and OC, with low concentrations enhancing expression and higher concentrations suppressing expression. The effects of Dex on osteoblast proliferation, differentiation, and mineralization were examined in the presence and absence of the ENaC specific antagonist amiloride. Dex at 10−8M and 10−6M markedly increased osteoblast proliferation, alkaline phosphatase activity (an index of differentiation), and calcium nodule formation, while 10−4M had no effect or suppressed all these responses. Amiloride blocked the Dex-induced, osteoblast differentiation and mineralization but had no effect on osteoblast differentiation and mineralization when applied alone. But such changes did not show in osteoblast proliferation. However, the Dex-induced α-ENaC expression was not blocked by RU486, a GC receptor antagonist.

Conclusion

These results suggest that changes in ENaC activity may involved in Dex-induced differentiation and mineralization of osteoblast. But the Dex-induced effect on ENaC did not mediated by the GC genomic mechanism in osteoblast at this study.

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Acknowledgments

Appreciation is expression to the co-workers of the Department of Hematology, First Affiliated Hospital, Sun Yat-Sen University, for assistance with data analyses. This research is supported by the National Natural Science Foundation of China (30971172); and by the Guangdong Natural Science Fund (8251022401000005).

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Author notes

  1. Qingnan Li

    Present address: Guangzhou Higher Education Mage Center, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Waihuan East Road 280#, Guangzhou, 510006, China

Authors and Affiliations

  1. Center of New Drug Function, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Li Lu, Liang Wu, Huanhuan Jia, Yingbing Li, Jun Chen & Qingnan Li

  2. Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou, 510006, People’s Republic of China

    Li Lu, Liang Wu, Huanhuan Jia, Yingbing Li, Jun Chen & Qingnan Li

  3. Department of Hematology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Duorong Xu

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  1. Li Lu
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Correspondence to Duorong Xu or Qingnan Li.

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Lu, L., Wu, L., Jia, H. et al. The epithelial sodium channel is involved in dexamethasone-induced osteoblast differentiation and mineralization. Cell Biol Toxicol 28, 279–289 (2012). https://doi.org/10.1007/s10565-012-9222-1

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  • DOI: https://doi.org/10.1007/s10565-012-9222-1

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