PPARγ Maintains Homeostasis through Autophagy Regulation in Dental Pulp.
This study investigated the relevance between pulp vitality and autophagy in aged human dental pulp cells (HDPCs) and whether peroxisome proliferator-activated receptor gamma (PPARγ) affects autophagy regulation for homeostasis in the aging progress. In vivo experiments were used in human and Sprague-Dawley rat teeth obtained from young and adult individuals. Aging- and autophagy-related molecules were determined by immunohistochemistry and hematoxylin and eosin staining. HDPCs were serially subcultured until spontaneously arrested for in vitro aging, and the replication deficiency adenovirus was introduced for PPARγ overexpression. Subsequently, the effect of PPARγ on regulation of autophagy molecules, mitochondria activity, and cell viability was assessed using Western blotting, confocal microscopy, and the MTT assay, respectively. In adult pulp tissue, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B light chain, and Beclin-1) were increased, but aging-related (PPARγ and heme oxygenase 1 [HO-1]) and dentinogenesis (dentin sialophosphoprotein and dentin matrix acidic phosphoprotein) molecules were decreased. In aged HDPCs, autophagy and intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were increased, while PPARγ and HO-1 were decreased. Under stimulation with lipopolysaccharide, autophagy- and aging-related molecules were differentially expressed between young and aged cells. PPARγ induced HO-1 and autophagy molecules but reduced inflammatory molecules in aged cells. In addition, PPARγ activated strong mitochondrial activity and cell viability in aging cells. Inhibition of HO-1 by tin protoporphyrin IX exacerbated autophagy and mitochondrial activity as well as cell viability in young cells. This study indicates that PPARγ maintains pulp homeostasis through the regulation of autophagy molecules during the life span of HDPCs.
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
Y H
YH
Lee
Department of Conservative Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
H Y
HY
Lee
Department of Conservative Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
T G
TG
Kim
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
N H
NH
Lee
Department of Conservative Dentistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea.
M K
MK
Yu
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Korea yihokn@chonbuk.ac.kr.
H K
HK
Yi
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000037:antagonists & inhibitors; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000032:analysis / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D051547:Heme Oxygenase-1; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D008869:Microtubule-Associated Proteins; D047495:PPAR gamma; D010750:Phosphoproteins; D011524:Protoporphyrins; D012795:Sialoglycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D000099311:Dentin Sialophosphoprotein; C032628:tin protoporphyrin IX
HDPCs; HO-1; aging; cell viability; dentinogenesis; mitochondria