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.
Guanghua School of Stomatology and Institute of Stomarological Research, Sun Yat-sen University, Lingyuan Xilu 56, Guangzhou, China.
Mu
M
Chen
Hong-Zhang
HZ
Huang
Miao
M
Wang
An-Xun
AX
Wang
D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D018507:Gene Expression Regulation, Developmental; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects*; D010159:Palate / Q000187:drug effects / Q000196:embryology*; D013723:Teratogens / Q000633:toxicity*; D014212:Tretinoin / Q000633:toxicity*; D015854:Up-Regulation
D003470:Culture Media; D013723:Teratogens; D014212:Tretinoin; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I