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The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification

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Abstract

Purpose

Mesenchymal progenitor cells (MPCs) are capable of differentiating into osteo/chondrogenic cells to contribute substantially to heterotopic ossification (HO). This study aimed to examine the impact of hypoxia on MPCs in the aetiology of HO.

Methods

MPCs from human normal and HO skeletal tissue were cultivated under normoxia and hypoxia. Gene expression of factors which have a key role in HO aetiology (BMPs, COX-1 and COX-2, etc.) were examined by real-time PCR. Tissue of both groups was analysed by immunohistochemistry.

Results

Under hypoxia, COX-1, -2 and SOX-9 gene expression was elevated in HO MPCs, whereas in normal muscle tissue only COX-2 was upregulated. MPCs from HO had a significantly elevated gene expression of BMP-4 and decreased expression of BMP-1 and HIF-1 under hypoxia compared to normal MPCs. Immunohistochemistry detected no significant differences between normal and HO tissue.

Conclusions

Hypoxia causes an enhanced gene expression of factors, which have a key role in HO pathophysiology. A better understanding of this entity will possibly allow reducing HO rates in orthopaedic and trauma surgery.

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Acknowledgments

The authors would like to thank Mr. Matthias Munding and Mrs. Nicole Richter for their excellent technical assistance and contribution to this study

Funding

This study was funded by the Medical Faculty of the University of Regensburg (ReFormA).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany

    Sebastian Winkler, Tanja Niedermair, Joachim Grifka, Susanne Grässel, Sven Anders, Guido Heers & Ferdinand Wagner

  2. Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany

    Tanja Niedermair & Susanne Grässel

  3. Department of Orthopaedic Surgery and Traumatology, Hospital Barmherzige Brüder, Regensburg, Germany

    Bernd Füchtmeier

Authors
  1. Sebastian Winkler
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  2. Tanja Niedermair
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  3. Bernd Füchtmeier
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  4. Joachim Grifka
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  5. Susanne Grässel
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  6. Sven Anders
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  7. Guido Heers
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  8. Ferdinand Wagner
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Correspondence to Sebastian Winkler.

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Winkler, S., Niedermair, T., Füchtmeier, B. et al. The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification. International Orthopaedics (SICOT) 39, 2495–2501 (2015). https://doi.org/10.1007/s00264-015-2995-0

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  • DOI: https://doi.org/10.1007/s00264-015-2995-0

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