title: G protein-coupled calcium-sensing receptor is a crucial mediator of MTA-induced biological activities.
abstract: Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs). We found that MTA activates diverse CaSR downstream pathways; notably, CaSR activation essentially requires dual modulation of extracellular Ca2+and pH via MTA. Among the CaSR downstream pathways, Ca2+mobilization from intracellular stores by the phospholipase C pathway plays an important role in osteogenic differentiation of hDPCs by regulating transcriptional activity. Our findings shed light on the signal transduction mechanism of MTA, thus providing a crucial molecular basis for the use of MTA in regenerative dental therapy.
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, South Korea.
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, South Korea.
authors.forename: Seulki
authors.initials: S
authors.lastname: Choi
authors.affiliation: Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, South Korea.
authors.forename: Kyu Hwan
authors.initials: KH
authors.lastname: Kwack
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, South Korea.
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, South Korea. Electronic address: kppark@snu.ac.kr.
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
mesh_terms: D000293:Adolescent; D017607:Aluminum Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017610:Calcium Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004338:Drug Combinations; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017640:Silicates / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D017607:Aluminum Compounds; D017610:Calcium Compounds; D004338:Drug Combinations; D010087:Oxides; D044169:Receptors, Calcium-Sensing; D017640:Silicates; C086631:mineral trioxide aggregate; D002118:Calcium
keywords: Calcium; Calcium sensing receptor; Dental pulp cell; Mineral trioxide aggregate; pH