title: C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.
abstract: Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases.
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Conservative Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Conservative Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Department of Oral Pathology, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: S D
authors.initials: SD
authors.lastname: Cho
authors.affiliation: Department of Preventive Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: J G
authors.initials: JG
authors.lastname: Jeon
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea yihokn@chonbuk.ac.kr.
authors.forename: H K
authors.initials: HK
authors.lastname: Yi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D003810:Dentinogenesis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005949:Glucose Oxidase / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D034741:RNA, Small Interfering; D005949:Glucose Oxidase; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AKT; AMPK; dentinogenesis; diabetes; oral complicated disease; pulp homeostasis