Chai Y, Bringas P, Mogharei A, Shuler C F, Slavkin H C
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033, USA.
Dev Dyn. 1998 Dec;213(4):500-11. doi: 10.1002/(SICI)1097-0177(199812)213:4<500::AID-AJA14>3.0.CO;2-A.
Platelet-derived growth factor A (PDGF-A) binding to the PDGF receptor alpha (PDGFR-alpha) mediates signal transduction processes related to DNA synthesis, cell migrations, cytodifferentiation, and wound healing. Recent studies indicate that PDGFR-alpha functions during cranial neural crest cell migrations and first branchial arch morphogenesis (Stephenson et al. [1991] Proc. Natl. Acad. Sci. USA 88:6-10; Morrison-Graham et al. [1992] Development 115:133-142; Hu et al. [1995] Int. J. Dev. Biol. 39:939-945; Soriano [1997] Development 124:2691-2700). The present studies were designed to test the hypothesis that PDGF-A, interacts with its cognate receptor PDGFR-alpha via an autocrine mechanism that regulates the timing, rates, and size of embryonic mouse tooth morphogenesis. Both PDGF-A and PDGFR-alpha transcripts were coordinately expressed in mandibular prominences prior to and during tooth formation using reverse transcriptase-polymerase chain reaction (RT-PCR). During the dental lamina stage, ligand and receptor were present in both enamel organ epithelium and adjacent mesenchymal cells. During the bud stage, ligand and receptor were localized mainly to the enamel organ epithelium. Exogenous PDGF-A at 20 ng/ml enhanced tooth development to reach the cap stage with increased tooth size (P < 0.05) using embryonic day (E)10 mandibular explants cultured in serumless, chemically defined medium. A significant increase in DNA synthesis was observed within enamel organ epithelium at E10+4 when the mandibular explants were treated with PDGF-A at 20 ng/ml. These data suggest that PDGF-A and its cognate receptor (PDGFR-alpha) regulate the size and stage of tooth development via an autocrine mechanism during odontogenesis in vitro.
血小板衍生生长因子A（PDGF-A）与血小板衍生生长因子受体α（PDGFR-α）结合，介导与DNA合成、细胞迁移、细胞分化和伤口愈合相关的信号转导过程。最近的研究表明，PDGFR-α在颅神经嵴细胞迁移和第一鳃弓形态发生过程中发挥作用（斯蒂芬森等人[1991年]《美国国家科学院院刊》88:6-10；莫里森-格雷厄姆等人[1992年]《发育》115:133-142；胡等人[1995年]《国际发育生物学杂志》39:939-945；索里亚诺[1997年]《发育》124:2691-2700）。本研究旨在检验以下假设：PDGF-A通过自分泌机制与其同源受体PDGFR-α相互作用，调节胚胎小鼠牙齿形态发生的时间、速率和大小。在牙齿形成之前和期间，使用逆转录聚合酶链反应（RT-PCR）在下颌突中协同表达PDGF-A和PDGFR-α转录本。在牙板阶段，配体和受体存在于釉器上皮和相邻的间充质细胞中。在芽阶段，配体和受体主要定位于釉器上皮。使用在无血清、化学成分明确的培养基中培养的胚胎第10天（E10）下颌外植体，20 ng/ml的外源性PDGF-A可促进牙齿发育至帽状期，牙齿大小增加（P < 0.05）。当用20 ng/ml的PDGF-A处理下颌外植体时，在E10+4时观察到釉器上皮内DNA合成显著增加。这些数据表明，在体外牙发生过程中，PDGF-A及其同源受体（PDGFR-α）通过自分泌机制调节牙齿发育的大小和阶段。
