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Updated: Feb 3, 2026
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their
Yi Liu1, Xiaoqing Ma2, Jing Guo1
1Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510140, China.
Introduction:
Alcoholism can lead to low mineral density, compromised regenerative bone capacity and delayed osteointegration of dental implants. This may be partially attributed to the inhibitive effect of all-trans retinoic acid (ATRA), a metabolite of alcohol, on osteoblastogenesis. Our previous studies demonstrated that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) was a more potent BMP than homodimeric BMP2 or BMP7, and could antagonize the inhibitive effect of ATRA to rescue osteoblastogenesis.
Materials And Methods:
In this study, we compared the effectiveness of BMP2/7, BMP2 and BMP7 in restoring osteoblastogenesis of murine preosteoblasts upon inhibition with 1 µM ATRA, and we further analyzed the potential mechanisms. We measured the following parameters: cell viability, ALP, OCN, mineralization, the expression of osteogenic differentiation marker genes (Collagen I, ALP and OCN) and the expression of BMP signaling key genes (Dlx5, Runx2, Osterix and Smad1).
Results:
BMP2/7 treatment alone induced significantly higher osteoblastogenesis compared to BMP2 and BMP7. When cells were treated by ATRA, BMP2/7 was superior only in rescuing cell viability and ALP activity, compared to BMP2 or BMP7. However, BMP2/7 was not superior to BMP2 or BMP7 in restoring OCN expression and extracellular mineralized nodules, or in rescuing expression of two key osteogenic genes, Dlx5 and Runx2. Irrespective of their dimeric types or potency, the selected BMPs could antagonize the inhibitory effect of ATRA on osteoblastogenesis.
Conclusion:
The presence of ATRA, BMP2/7 still induced significantly higher cell viability and early differentiation than the homodimers. However, ATRA significantly attenuated the advantages of BMP2/7 in inducing late and final osteoblastogenic differentiation over the homodimers.
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