The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification
The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification
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DOI：
10.1007/s00264-015-2995-0
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发表时间：
2015-10
影响因子：
2.7
通讯作者：
S. Winkler;T. Niedermair;B. Füchtmeier;J. Grifka;S. Grässel;S. Anders;G. Heers;F. Wagner
中科院分区：
文献类型：
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作者：
S. Winkler;T. Niedermair;B. Füchtmeier;J. Grifka;S. Grässel;S. Anders;G. Heers;F. Wagner
目的：间充质祖细胞（MPCs）能够分化为成骨/软骨细胞，在异位骨化（HO）中起重要作用。本研究旨在探讨缺氧对HO病因中MPCs的影响。方法分别在常氧和缺氧条件下培养人正常和HO骨组织的smpcs。实时荧光定量PCR检测HO发病关键因子（bmp、COX-1、COX-2等）的基因表达情况。免疫组化分析两组组织。结果缺氧条件下，COX-1、COX-2和cox -9基因在HO MPCs中表达升高，而在正常肌肉组织中只有COX-2表达上调。与正常MPCs相比，缺氧条件下HO MPCs的BMP-4基因表达明显升高，BMP-1和HIF-1基因表达明显降低。免疫组化检测正常组织与HO组织无明显差异。结论缺氧可引起一些在HO病理生理中起关键作用的基因表达增强。更好地了解这个实体可能会降低骨科和创伤手术的HO率。
PurposeMesenchymal 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.MethodsMPCs 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.ResultsUnder 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.ConclusionsHypoxia 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.