Sebastian Winkler1, Tanja Niedermair2,3, Bernd Füchtmeier4, Joachim Grifka5, Susanne Grässel6,7, Sven Anders8, Guido Heers9, Ferdinand Wagner10. 1. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. sebastianwinkler@email.de. 2. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Tanja.Niedermair@klinik.uni-regensburg.de. 3. Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany. Tanja.Niedermair@klinik.uni-regensburg.de. 4. Department of Orthopaedic Surgery and Traumatology, Hospital Barmherzige Brüder, Regensburg, Germany. Bernd.Fuechtmeier@barmherzige-regensburg.de. 5. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Joachim.Grifka@ukr.de. 6. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Susanne.Graessel@klinik.uni-regensburg.de. 7. Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany. Susanne.Graessel@klinik.uni-regensburg.de. 8. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Sven.Anders@ukr.de. 9. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Guido.Heers@ukr.de. 10. Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Ferdinand.Wagner@ukr.de.
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.
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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