FAXDC2 (fatty acid hydroxylase domain containing 2) is a member of the fatty acid hydroxylase superfamily. Given the important role of fatty acids in megakaryocytes, we have studied the role of this gene in the development of this lineage. Here we show that the expression of FAXDC2 is constantly elevated during megakaryocyte maturation. In contrast, FAXDC2 is significantly downregulated in acute myeloid leukemia and acute megakaryoblastic leukemia. Moreover, FAXDC2 overexpression promotes the differentiation of megakaryocytic cell lines and primary cells, whereas its knockdown disrupts their maturation. Mechanism study shows that FAXDC2 overexpression enhances extracellular signal-regulated kinase (ERK) signaling and increases RUNX1 (Runt-related transcription factor 1) expression. FAXDC2 also restores megakaryocytic differentiation in cells exposed to an ERK inhibitor or those expressing a dominant negative form of RUNX1. Finally, FAXDC2 overexpression leads to an increase in sphingolipid GM3 synthase, suggesting a potential role of FAXDC2 in lipid metabolism that increases ERK signaling and facilitates megakaryocyte differentiation. Together, these results show that FAXDC2 plays a novel role in development of megakaryocytes and its dysregulation may contribute to abnormal hematopoietic cell development in leukemia.
Biomimetics inspired by superstructures and extraordinary properties of teeth have resulted in tooth repair and the generation of novel materials. However, little attention has been paid to tooth color, whose origin remains unknown. Based on recent studies, fluorophores-mainly aromatic amino acids (AAAs) in proteins-might be responsible for tooth color. We synthesized carbonated hydroxyapatite (HA; the mineral phase of teeth) in the presence of different amino acids (AAs; the basic units of protein matrix of teeth) as a simplified model of teeth to explore the color source at the AA level. After measuring the fluorescence and color characteristics of HA-AAs before and after bleaching treatment, we found that only HA, synthesized in the presence of AAAs, exhibited remarkable fluorescence and color property. Furthermore, linearly increased fluorescence intensity and deeper color were observed with an increase in AAA content in HA-AAAs. Similarly, significantly decreased absorbance of HA-AAAs between 250 and 300 nm in ultraviolet spectra, declined fluorescence intensity, and decolored performance of HA-AAAs were observed after bleaching treatment. The results showed that AAAs contributed to the fluorescence and color properties of HA and that hydrogen peroxide might whiten HA-AAAs by oxidizing the benzene ring in AAAs. These findings are of great significance in promoting the synthesis of advanced tooth-colored materials and furthering our understanding of the possible mechanisms of hydrogen peroxide. Moreover, our study shed light on the importance of AAAs and might provide new ideas for investigations of biomineralization and biomimetics.
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