The role of heme oxygenase-1 in the proliferation and odontoblastic differentiation of human dental pulp cells.
BACKGROUND
It was recently reported that heme oxygenase-1 (HO-1) activity is related to stem cell differentiation; however, the involvement of HO-1 in pulp cell growth and differentiation has not been well explored. The purpose of this study was to investigate the role of HO-1 in the growth and differentiation of human dental pulp cells (HDPCs).


METHODS
We evaluated cell growth by MTT assay, mineralization by alizarin red staining, and differentiation marker mRNA expression by reverse transcriptase polymerase chain reaction.


RESULTS
HO-1 induction by cobaltic protoporphyrin IX (CoPP) in HDPCs increased cell growth and mineralization and up-regulated the messenger RNA expression of such odontoblastic markers as alkaline phosphatase, osteopontin, bone sialoprotein, dentin matrix protein-1, and dentin sialophosphoprotein. Carbon monoxide scavenger, iron chelator, HO-1 inhibitor, and HO-1 small interfering RNA (siRNA) attenuated HDPC growth and differentiation.


CONCLUSIONS
CoPP treatment results in dental pulp cell proliferation and odontoblast differentiation that appears partly mediated by HO-1. Our results suggest that odontoblastic differentiation and growth are positively regulated by HO-1 induction and negatively regulated by HO-1 inhibition. Thus, pharmacologic HO-1 induction might represent a potent therapeutic approach for pulp capping and the regeneration of HDPCs.
Kim
Sun-Ju
SJ
Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, Iksan City, Jeonbuk, 570-749, South Korea.
Min
Kyung-San
KS
Ryu
Hyun-Wook
HW
Lee
Hwa-Jeong
HJ
Kim
Eun-Cheol
EC
D000469:Alkaline Phosphatase / Q000032:analysis; D000880:Anthraquinones; D002113:Calcification, Physiologic / Q000502:physiology; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D016166:Free Radical Scavengers / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D007502:Iron Chelating Agents / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D009804:Odontoblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D053495:Osteopontin / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000032:analysis; D013778:Tetrazolium Salts; D013844:Thiazoles; D015854:Up-Regulation; D000099311:Dentin Sialophosphoprotein
D000469:Alkaline Phosphatase; D000880:Anthraquinones; D002248:Carbon Monoxide; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D016166:Free Radical Scavengers; D051547:Heme Oxygenase-1; D058574:Integrin-Binding Sialoprotein; D007502:Iron Chelating Agents; D008665:Metalloporphyrins; D053495:Osteopontin; D010750:Phosphoproteins; D011524:Protoporphyrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012795:Sialoglycoproteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C546871:IBSP protein, human; C010078:alizarin; C007095:cobaltiprotoporphyrin; C032628:tin protoporphyrin IX; C022616:thiazolyl blue