Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

• Published in: Cellular physiology and biochemistry Vol. 43; no. 6; pp. 2535 - 2547
• Main Authors: Wang, Xuan, Wu, Tian Tian, Jiang, Long, Rong, Du, Zhu, Ya Qin
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adolescent; Apoptosis; Autophagy; Autophagy - drug effects; Autophagy-Related Protein 5 - antagonists & inhibitors; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Beclin-1 - metabolism; Biomedical materials; Cancer; Cell biology; Cell differentiation; Cell Differentiation - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Deferoxamine - pharmacology; Dental pulp; Dental Pulp - cytology; Endodontics; Homeostasis; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Macrolides - pharmacology; Membrane Proteins - metabolism; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - metabolism; Mineralization; Odontoblasts - cytology; Odontoblasts - metabolism; Odontogenesis; Proto-Oncogene Proteins - metabolism; Pulp biology; Reactive Oxygen Species - metabolism; Regeneration; Retracted Paper; RNA Interference; RNA, Small Interfering - metabolism; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Tissue engineering; Young Adult; United States > US; Odontogenesis; Cell biology; Regeneration; Endodontics; Cell differentiation; Pulp biology
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000484506

As a vital degradation and recycling system, autophagy plays an essential role in regulating the differentiation of stem cells. We previously showed that iron chelator deferoxamine (DFO) could promote the repair ability of dental pulp stem cells (DPSCs). Here, we investigated the effect of DFO in autophagy and the role of autophagy in regulating the migration and odontoblast differentiation of DPSCs. Transmission electron microscopy, immunofluorescence staining and western blotting were performed to evaluate the autophagic activity of DPSCs. Transmigration assay, alkaline phosphatase staining/activity, alizarin red S staining and quantitative PCR were performed to examine the migration and odontoblast differentiation of DPSCs. Reactive oxygen species (ROS) levels and the effects of ROS scavenger in autophagy induction were also detected. Autophagy inhibitors (3-MA and bafilomycin A1) and lentiviral vectors carrying ATG5 shRNA sequences were used for autophagy inhibition. Early exposure to DFO promoted the mineralization of DPSCs and increased autophagic activity. Autophagy inhibition suppressed DFO-induced DPSC migration and odontoblast differentiation. Furthermore, DFO treatment could induce autophagy partly through hypoxia-inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K-interacting protein 3 (HIF-1α/BNIP3) pathway in a ROS-dependent manner. DFO increased DPSC migration and differentiation, which might be modulated through ROS-induced autophagy.