Abstract
Transforming growth factor β1 (TGF-β1) and Runt-related transcription factor 2 (RUNX2) are critical factors promoting enamel development and maturation. Our previous studies reported that absence of TGF-β1 or RUNX2 resulted in abnormal secretion and absorption of enamel matrix proteins. However, the mechanism remained enigmatic. In this study, TGF-β1−/−Runx2−/− and TGF-β1+/−Runx2+/− mice were successfully generated to clarify the relationship between TGF-β1 and RUNX2 during amelogenesis. Lower mineralization was observed in TGF-β1−/−Runx2−/− and TGF-β1+/−Runx2+/− mice than single gene deficient mice. Micro-computed tomography (μCT) revealed a lower ratio of enamel to dentin density in TGF-β1−/−Runx2−/− mice. Although μCT elucidated a relatively constant enamel thickness, variation was identified by scanning electron microscopy, which revealed that TGF-β1−/−Runx2−/− mice were more vulnerable to acid etching with lower degree of enamel mineralization. Furthermore, the double gene knock-out mice exhibited more serious enamel dysplasia than the single gene deficient mice. Hematoxylin–eosin staining revealed abnormalities in ameloblast morphology and arrangement in TGF-β1−/−Runx2−/− mice, which was accompanied by the absence of atypical basal lamina (BL) and the ectopic of enamel matrix. Odontogenesis-associated phosphoprotein (ODAPH) has been identified as a component of an atypical BL. The protein and mRNA expression of ODAPH were down-regulated. In summary, TGF-β1 and RUNX2 might synergistically regulate enamel mineralization through the downstream target gene Odaph. However, the specific mechanism by which TGF-β1 and RUNX2 promote mineralization remains to be further studied.
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This work was supported by the National Natural Science Foundation of China (Grant Nos. 81670954, 81870738).
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Tian, Y., Mu, H., Dong, Z. et al. The synergistic effects of TGF-β1 and RUNX2 on enamel mineralization through regulating ODAPH expression during the maturation stage. J Mol Histol 53, 483–492 (2022). https://doi.org/10.1007/s10735-022-10060-2
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DOI: https://doi.org/10.1007/s10735-022-10060-2