Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Jiangsu Province, People's Republic of China.
Cell Tissue Res. 2012 Dec;350(3):425-37. doi: 10.1007/s00441-012-1487-4. Epub 2012 Sep 7.
Previous studies have shown that craniofacial bone marrow stromal cells (BMSCs) have a strong osteogenic potential. However, the mechanism by which BMSCs of various embryonic origins develop diverse osteogenic potentials remains unclear. To investigate the mechanisms regulating osteoblast differentiation in two different types of BMSCs, we compared the temporal and spatial mRNA and protein expression patterns of Satb2 and its downstream gene Hoxa2 by using real-time polymerase chain reaction, Western blotting and fluorescent immunostaining in mandible BMSCs (M-BMSCs) and tibia BMSCs (T-BMSCs) undergoing osteoblast differentiation. Higher levels of alkaline phosphatase, greater calcium accumulation and earlier expression of Runx2 were observed in osteogenic-induced M-BMSCs compared with T-BMSCs. Low levels of Satb2 were detected in both types of uninduced BMSCs but the majority of SATB2 was located in the nuclei of M-BMSCs. Notably, Satb2 was expressed earlier in M-BMSCs and Hoxa2, a downstream target of Satb2, was not expressed in uninduced M-BMSCs or during osteoblast differentiation, just as during embryonic mandible development. In contrast, Hoxa2 was reactivated in T-BMSCs during osteoblast differentiation. Based on these results, we conclude that SATB2 plays a different role during osteoblast differentiation of M-BMSCs and T-BMSCs. The earlier activation of Satb2 expression in M-BMSCs compared with T-BMSCs might explain the stronger osteogenic potential of M-BMSCs.
先前的研究表明颅面骨髓基质细胞（BMSCs）具有很强的成骨潜能。然而，各种胚胎起源的 BMSCs 如何发展出不同的成骨潜能的机制尚不清楚。为了研究调节两种不同类型 BMSCs 成骨细胞分化的机制，我们通过实时聚合酶链反应、Western blot 和荧光免疫染色比较了下颌骨 BMSCs（M-BMSCs）和胫骨 BMSCs（T-BMSCs）中成骨诱导过程中 Satb2 及其下游基因 Hoxa2 的时空 mRNA 和蛋白表达模式。与 T-BMSCs 相比，成骨诱导的 M-BMSCs 中碱性磷酸酶水平更高，钙积累更多，Runx2 表达更早。在未诱导的两种 BMSCs 中，Satb2 的水平均较低，但 SATB2 的大部分位于 M-BMSCs 的核内。值得注意的是，Satb2 在 M-BMSCs 中更早表达，而其下游靶点 Hoxa2 在未诱导的 M-BMSCs 中或成骨细胞分化过程中均不表达，就像在胚胎下颌骨发育过程中一样。相反，Hoxa2 在 T-BMSCs 成骨细胞分化过程中被重新激活。基于这些结果，我们得出结论，SATB2 在 M-BMSCs 和 T-BMSCs 的成骨细胞分化中发挥不同的作用。与 T-BMSCs 相比，M-BMSCs 中 Satb2 表达的更早激活可能解释了 M-BMSCs 更强的成骨潜能。
