Sox9 Modulates Proliferation and Expression of Osteogenic Markers of Adipose-Derived Stem Cells (ASC)
Sox9 Modulates Proliferation and Expression of Osteogenic Markers of Adipose-Derived Stem Cells (ASC)
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DOI：
10.1159/000350089
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发表时间：
2013-05
影响因子：
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通讯作者：
S. Stöckl;C. Göttl;J. Grifka;S. Grässel
中科院分区：
文献类型：
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作者：
S. Stöckl;C. Göttl;J. Grifka;S. Grässel
背景：间充质干细胞（MSC）是组织工程和肌肉骨骼再生的重要工具。它们存在于各种组织中，如脂肪组织、骨膜、滑液、肌肉、真皮、血液和骨髓，后者是用于MSC分离的最常见组织。MSC的一个有前途的替代来源是脂肪组织，因为与骨髓相比，MSC的可用性更好，产量更高。一个缺点是脂肪来源的干细胞（ASC）生理学的知识还不完整，以便使它们成为体内应用的安全工具。方法/结果：在这里，我们确定了Sox 9作为一个高表达和关键的转录因子在未分化大鼠ASC（rASC）。与大鼠骨髓源性干细胞（rBMSC）相比，Sox 9的mRNA和蛋白水平在rASC中显著更高。为了详细研究Sox 9的作用，我们在rASC中用shRNA沉默Sox 9，并检查了增殖、凋亡和成骨分化标志物的表达。我们的研究结果清楚地表明，未分化的rASC和rBMSC在早期传代中成骨标志物基因的表达谱存在差异。Sox 9基因沉默可诱导骨钙素、VEGFα和Mmp 13的表达，并抑制rASC增殖，同时诱导p21和cyclin D1的表达，延迟进入S期。结论：我们认为Sox 9在未分化的rASC中具有促增殖作用，这可以解释rASC与rBMSC相比具有更高的增殖率。此外，我们提出了一个成骨分化延迟作用的Sox 9在rASC，这表明，Sox 9的表达是需要维持rASC在未分化，增殖状态。
Background: Mesenchymal stem cells (MSC) are promising tools for tissue-engineering and musculoskeletal regeneration. They reside within various tissues, like adipose tissue, periosteum, synovia, muscle, dermis, blood and bone marrow, latter being the most common tissue used for MSC isolation. A promising alternative source for MSC is adipose tissue due to better availability and higher yield of MSC in comparison to bone marrow. A drawback is the yet fragmentary knowledge of adipose-derived stem cell (ASC) physiology in order to make them a safe tool for in vivo application. Methods/Results: Here, we identified Sox9 as a highly expressed and crucial transcription factor in undifferentiated rat ASC (rASC). In comparison to rat bone marrow-derived stem cells (rBMSC), mRNA and protein levels of Sox9 were significantly higher in rASC. To study the role of Sox9 in detail, we silenced Sox9 with shRNA in rASC and examined proliferation, apoptosis and the expression of osteogenic differentiation markers. Our results clearly point to a difference in the expression profile of osteogenic marker genes between undifferentiated rASC and rBMSC in early passages. Sox9 silencing induced the expression of osteocalcin, Vegfα and Mmp13, and decreased rASC proliferation accompanied with an induction of p21 and cyclin D1 expression and delayed S-phase entry. Conclusions: We suggest a pro-proliferative role for Sox9 in undifferentiated rASC which may explain the higher proliferation rate of rASC compared to rBMSC. Moreover, we propose an osteogenic differentiation delaying role of Sox9 in rASC which suggests that Sox9 expression is needed to maintain rASC in an undifferentiated, proliferative state.