Chen Mu, Huang Hong-Zhang, Wang Miao, Wang An-Xun
Guanghua School of Stomatology and Institute of Stomarological Research, Sun Yat-sen University, Lingyuan Xilu 56, Guangzhou, China.
Birth Defects Res A Clin Mol Teratol. 2010 Nov;88(11):965-70. doi: 10.1002/bdra.20723.
All-trans-retinoic acid (ATRA), a known teratogenic factor affecting the development of cleft palate, has been shown to adversely affect craniofacial development. In the present study, we evaluated the effects of ATRA on the osteo-/adipogenic differentiation of mouse embryonic palate mesenchymal (MEPM) cells, which served as a valid model system for investigating the mechanisms regulating osteogenesis during palatogenesis.
MEPM cells were derived from gestational day 13 C57BL/6N mouse embryos and induced to differentiate in the presence or absence of ATRA in either osteogenic medium (OM) or control medium (CM).
Alkaline phosphatase (ALP) activity assays, von Kossa staining, and RT-PCR assays confirmed that MEPM cells underwent osteogenic differentiation when cultured in OM. Although ATRA induced ALP activity and lipid accumulation in MEPM cells, it failed to induce matrix mineralization and osteoblastic gene expression. BMPR-IB and Smad5 mRNA levels increased significantly in cells cultured in OM and declined following treatment with ATRA, whereas the expression of the BMPR-IA mRNA was up-regulated by ATRA.
In conclusion, our results suggested that ATRA and the BMP signaling pathway cooperate to inhibit osteogenesis and promote adipogenesis of MEPM cells.
全反式维甲酸（ATRA）是一种已知的影响腭裂发育的致畸因子，已被证明会对颅面发育产生不利影响。在本研究中，我们评估了ATRA对小鼠胚胎腭间充质（MEPM）细胞成骨/成脂分化的影响，MEPM细胞是研究腭发育过程中调节骨生成机制的有效模型系统。
MEPM细胞来源于妊娠第13天的C57BL/6N小鼠胚胎，在成骨培养基（OM）或对照培养基（CM）中，在有或无ATRA的情况下诱导分化。
碱性磷酸酶（ALP）活性测定、冯科萨染色和RT-PCR测定证实，MEPM细胞在OM中培养时经历了成骨分化。虽然ATRA诱导了MEPM细胞中的ALP活性和脂质积累，但它未能诱导基质矿化和成骨细胞基因表达。在OM中培养的细胞中，BMPR-IB和Smad5 mRNA水平显著增加，而用ATRA处理后下降，而BMPR-IA mRNA的表达则被ATRA上调。
总之，我们的结果表明，ATRA和BMP信号通路协同抑制MEPM细胞的成骨作用并促进其成脂作用。
