Pannexin 3, a gap junction protein, regulates proliferation through AMPK pathway in odontoblasts

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Pannexin 3 (Panx3), a member of the pannexin family of gap junction proteins, regulates chondrocyte and osteoblast differentiation. However, its expression and physiological functions in tooth development remain unclear. Our objective was to elucidate the expression and identification of molecular mechanisms of Panx3 functions in tooth development. In situ hybridization demonstrated that Panx3 mRNA was preferentially expressed in preodontoblasts. To analyze the role of Panx3 in odontoblast proliferation and differentiation, we used the odontogenic cell line mDP. We found that Panx3 expression was induced in differentiating mDP cells, and overexpression of Panx3 inhibited mDP cell proliferation and promoted cell differentiation into odontoblasts. We also found that Panx3 overexpression promoted the release of ATP into the extracellular space and induced the phosphorylation of AMP activated protein kinase (AMPK), a highly conserved energy sensor in all eukaryotic cells. Further, the activated AMPK pathway inhibited mDP cell proliferation and induced p21 expression. Taken together, our results suggest that Panx3 reduces intracellular ATP levels through a hemichannel, which results in inhibition of odontoblast proliferation though the AMPK/p21 pathway.(Supported by grants from the Ministry of Education, Science, and Culture of Japan and the Intramural Program of the NIDCR, NIH, USA)