| First Author | Okubo M | Year | 2019 |
| Journal | J Oral Biosci | Volume | 61 |
| Issue | 1 | Pages | 43-54 |
| PubMed ID | 30929801 | Mgi Jnum | J:290672 |
| Mgi Id | MGI:6443234 | Doi | 10.1016/j.job.2018.12.002 |
| Citation | Okubo M, et al. (2019) Potential function of TGF-beta isoforms in maturation-stage ameloblasts. J Oral Biosci 61(1):43-54 |
| abstractText | OBJECTIVES: To investigate potential functions of transforming growth factor-beta (TGF-beta) isoforms in maturation-stage ameloblasts during amelogenesis. METHODS: In vivo activation of TGF-beta was characterized by using matrix metalloproteinase 20 null (Mmp20(-/-)) and wild-type (Mmp20(+/+)) mice. Using mHAT9d cells cultured in the presence of each TGF-beta isoform, (1) cell proliferation was determined by MTS assay, (2) immunostaining with anti-cleaved caspase-3 monoclonal antibody was performed and apoptotic indices were measured, (3) gene expression was analyzed by RT-qPCR, and (4) the uptake of amelogenin into mHAT9d cells was directly observed using a fluorescence microscope. RESULTS: TGF-beta1 and TGF-beta3 were present in the enamel matrix of developing teeth which were activated by MMP20 in vivo. A genetic study revealed that the three TGF-beta isoforms upregulate kallikrein 4 (KLK4) mRNA levels but downregulate carbonic anhydrase II. Moreover, TGF-beta1 and TGF-beta2 significantly upregulated the mRNA level of amelotin, whereas TGF-beta3 dramatically downregulated the mRNA levels of odontogenic ameloblast-associated protein (ODAM), family with sequence similarity 83 member H (FAM83H), and alkaline phosphatase (ALP). Immunostaining analysis showed that the apoptosis of mHAT9d cells is induced by three TGF-beta isoforms, with TGF-beta3 being most effective. Both TGF-beta1 and TGF-beta3 induced endocytosis of amelogenin. CONCLUSIONS: We propose that TGF-beta is regulated in an isoform-specific manner to perform multiple biological functions such as gene expression related to the structure of basal lamina/ameloblasts, mineral ion transport, apoptosis, and endocytosis in maturation-stage ameloblasts. |
