title: The Role of ORAI1 in the Odontogenic Differentiation of Human Dental Pulp Stem Cells.
abstract: Pulp capping, or placing dental materials directly onto the vital pulp tissues of affected teeth, is a dental procedure that aims to regenerate reparative dentin. Several pulp capping materials are clinically being used, and calcium ion (Ca(2+)) released from these materials is known to mediate reparative dentin formation. ORAI1 is an essential pore subunit of store-operated Ca(2+) entry (SOCE), which is a major Ca(2+) influx pathway in most nonexcitable cells. Here, we evaluated the role of ORAI1 in mediating the odontogenic differentiation and mineralization of dental pulp stem cells (DPSCs). During the odontogenic differentiation of DPSCs, the expression of ORAI1 increased in a time-dependent manner. DPSCs knocked down with ORAI1 shRNA (DPSC/ORAI1sh) or overexpressed with dominant negative mutant ORAI1(E106Q) (DPSC/E106Q) exhibited the inhibition of Ca(2+) influx and suppression of odontogenic differentiation and mineralization as demonstrated by alkaline phosphatase (ALP) activity/staining as well as alizarin red S staining when compared with DPSCs of their respective control groups (DPSC/CTLsh and DPSC/CTL). The gene expression for odontogenic differentiation markers such as osteocalcin, bone sialoprotein, and dentin matrix protein 1 (DMP1) was also suppressed. When DPSC/CTL or DPSC/E106Q cells were subcutaneously transplanted into nude mice, DPSC/CTL cells induced mineralized tissue formation with significant increases in ALP and DMP1 staining in vivo, whereas DPSC/E106Q cells did not. Collectively, our data showed that ORAI1 plays critical roles in the odontogenic differentiation and mineralization of DPSCs by regulating Ca(2+) influx and that ORAI1 may be a therapeutic target to enhance reparative dentin formation.
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sohn
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Srikanth
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Arai
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Song
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: K-H
authors.initials: KH
authors.lastname: Shin
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Kang
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gwack
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: N-H
authors.initials: NH
authors.lastname: Park
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA, USA Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA rkim@dentistry.ucla.edu.
authors.forename: R H
authors.initials: RH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D003782:Dental Pulp / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D000071740:ORAI1 Protein; D009805:Odontogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human
keywords: calcium; calcium release-activated calcium (CRAC) channels; odontogenic mineralization; pulp capping; reparative dentin formation; store-operated calcium entry (SOCE)