Retinoic Acid Inhibits Osteogenic Differentiation of Mouse Embryonic Palate Mesenchymal Cells

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: In conclusion, our results suggested that ATRA and the BMP signaling pathway cooperate to inhibit osteogenesis and promote adipogenesis of MEPM cells. Birth Defects Research (Part A) 88: 965-970, 2010. (C) 2010 Wiley-Liss, Inc.