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Dexamethasone induces osteogenesis via regulation of hedgehog signalling molecules in rat mesenchymal stem cells

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Abstract

Purpose

Hedgehog signalling plays an important role during the development of tissues and organs, including bone and limb. Dexamethasone (DEX), a synthetic and widely used glucocorticoid, affects osteogenesis of bone marrow mesenchymal stem cells (MSCs), while the signalling pathway by which DEX affects osteoblast differentiation remains obscure. This study aimed to investigate expressions of hedgehog signalling molecules Shh, Ihh and Gli1 during DEX-induced osteogenesis of rat MSCs in vitro.

Methods

DEX promoted osteoblast differentiation of MSCs at 10−8 mol/L from seven days to 21 days, demonstrated by enhancing alkaline phosphatase (ALP) activity and osteoblast-associated marker type I collagen expression during osteoblastic differentiation. Gene and protein expressions of hedgehog signalling molecules, Shh, Ihh and Gli1 were tested by RT-PCR and western blot analysis during osteoblast differentiation.

Results

Shh expression was increased compared to the control while Ihh and Gli1 expressions were decreased on both mRNA and protein level during DEX-induced osteoblast differentiation of MSCs from seven days to 21 days. Altogether, these data demonstrate that DEX can enhance Shh expression via a Gli1-independent mechanism during osteoblast differentiation of MSCs.

Conclusions

These results indicate that different patterns of hedgehog signalling are involved in DEX-induced osteogenesis and these findings provide insights into the mechanistic link between glucocorticoid-induced osteogenesis and hedgehog signalling pathway.

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Acknowledgments

This work was funded by grants from the National Natural Science Foundation of China (No.81272588), Shandong Provincial Natural Science Foundation, China (No.ZR2012HM061), the Eduction Bureau of Shandong Province (J11LC14) and 973 Project grant (2012CB966503 and 2012CB966504).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China

    Xiaoli Ma, Yanfei Jia, Shanshan Zu, Shuyi Han, Dongjie Xiao & Yunshan Wang

  2. Shandong Research Center of Implantation and Tissue Engineering, Jinan, 250013, China

    Xiaoli Ma, Yanfei Jia, Dongjie Xiao & Yunshan Wang

  3. Shengdu Middle School of Shouguang, Shandong, 262700, China

    Xueping Zhang

  4. College of Life Science, Shandong Normal University, Jinan, 250014, China

    Haiji Sun

  5. Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People’s Republic of China

    Yunshan Wang

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  1. Xiaoli Ma
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  2. Xueping Zhang
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  3. Yanfei Jia
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  4. Shanshan Zu
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Corresponding authors

Correspondence to Haiji Sun or Yunshan Wang.

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Ma, X., Zhang, X., Jia, Y. et al. Dexamethasone induces osteogenesis via regulation of hedgehog signalling molecules in rat mesenchymal stem cells. International Orthopaedics (SICOT) 37, 1399–1404 (2013). https://doi.org/10.1007/s00264-013-1902-9

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  • DOI: https://doi.org/10.1007/s00264-013-1902-9

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