Wnt5a regulates dental follicle stem/progenitor cells of the periodontium.
Wnt5a regulates dental follicle stem/progenitor cells of the periodontium.
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DOI：
10.1186/scrt525
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发表时间：
2014-12-15
影响因子：
7.5
通讯作者：
Ling J
中科院分区：
文献类型：
--
作者：
Xiang L;Chen M;He L;Cai B;Du Y;Zhang X;Zhou C;Wang C;Mao JJ;Ling J
牙囊形成牙周组织中的一个或几个组织，包括牙周膜、牙骨质和/或牙槽骨。Wnt5a是否在出生后牙周组织中表达或调控牙囊干/祖细胞尚不清楚。从出生后第1天(第1天)至第11天从大鼠下颌第一磨牙分离牙囊干/祖细胞。免疫定位显示Wnt5a在牙槽骨、牙周膜、发育中的成釉细胞和成牙本质细胞层中均有表达。从p7牙囊中分离出单核细胞和贴壁细胞。为研究Wnt5A在牙囊干/祖细胞中的高表达，以天然牙囊干/祖细胞亚群为对照，采用实时定量聚合酶链式反应(Taqman)、Lenti病毒转染法、Western blotting和免疫荧光等方法研究其增殖、成骨分化和迁移行为。Wnt5A在p1~p11大鼠牙周持续表达。天然的p7牙囊干/祖细胞在测试的14天内具有中等的矿化能力。即使在化学成分明确的成骨介质中，牙囊干/祖细胞也只表现出适度的矿化。在成骨培养液中加入300 ng/mLWnt5a蛋白后，牙囊干/祖细胞矿化仍不明显。化学诱导和Wnt5a诱导的牙囊细胞矿化现象较少。Wnt5a与100 ng/mLBMP2联合使用，最终促进牙囊干/祖细胞产生强大的矿化，并上调Runx2、碱性磷酸酶、胶原蛋白1α1和骨钙素的表达。因此，天然牙囊干/祖细胞或它们的一部分在矿化方面可能是适度的。值得注意的是，Wnt5a蛋白显著增加了RANKL配体，提示牙囊干/祖细胞对单核/破骨细胞谱系的调节作用，并可能参与牙槽骨重建和/或吸收。在WNT5a过表达的牙囊细胞中，p-JNK1/2被激活；相反，在有或没有WNT5a的情况下，暴露于c-jun氨基末端激酶抑制剂SP600125可减弱Runx2、胶原1α1和骨钙素的表达。Wnt5A在牙囊干/祖细胞中的过表达显著降低了其增殖率，但显著增强了其迁移能力。这些发现使我们得以一窥Wnt5a在牙囊干/祖细胞和牙周组织中的可能作用，并在牙周病、牙齿萌出、种植体骨愈合和正畸牙齿移动中发挥作用。
Dental follicle gives rise to one or several tissues of the periodontium including the periodontal ligament, cementum and/or alveolar bone. Whether Wnt5a is expressed in the postnatal periodontium or regulates dental follicle stem/progenitor cells is unknown. Dental follicle stem/progenitor cells were isolated from postnatal day 1 (p1) to p11 from rat mandibular first molars. Immunolocalization mapped Wnt5a expression in the alveolar bone, periodontal ligament, and the developing ameloblast and odontoblast layers. Mononucleated and adherent cells were isolated from p7 dental follicle. Wnt5a was overexpressed in dental follicle stem/progenitor cells to study their proliferation, osteogenic differentiation and migration behavior, with subpopulations of native dental follicle stem/progenitor cells as controls, using real-time PCR (Taqman), Lenti-viral transfection, Western blotting and immunofluorescence. Wnt5a was expressed consistently in p1 to p11 rat peridontium. Native, p7 dental follicle stem/progenitor cells had modest ability to mineralize in the tested 14 days. Even in chemically defined osteogenesis medium, dental follicle stem/progenitor cells only showed modest mineralization. Upon addition of 300 ng/mL Wnt5a protein in osteogenesis medium, dental follicle stem/progenitor cells displayed mineralization that was still unremarkable. Chemically induced or Wnt5a-induced mineralization of dental follicle cells only occurred sparsely. Combination of Wnt5a with 100 ng/mL BMP2 finally prompted dental follicle stem/progenitor cells to produce robust mineralization with elevated expression of Runx2, alkaline phosphatase, collagen 1α1 and osteocalcin. Thus, native dental follicle stem/progenitor cells or some of their fractions may be somewhat modest in mineralization. Strikingly, Wnt5a protein significantly augmented RANKL ligand, suggesting putative regulatory roles of dental follicle stem/progenitor cells for the monocyte/osteoclast lineage and potential involvement in alveolar bone remodeling and/or resorption. P-Jnk1/2 was activated in Wnt5a overexpressed dental follicle cells; conversely, exposure to SP600125, a c-Jun N-terminal kinase (JNK) inhibitor attenuated Runx2, collagen 1α1 and osteocalcin expression either in the presence or absence of Wnt5a. Wnt5a overexpression in dental follicle stem/progenitor cells significantly reduced their proliferation rates, but robustly augmented their migration capacity. These findings provide a glimpse of Wnt5a’s putative roles in dental follicle stem/progenitor cells and the periodontium with implications in periodontal disease, tooth eruption, dental implant bone healing and orthodontic tooth movement.
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影响因子：
23.9
作者：
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通讯作者：
Grompe, Markus
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
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影响因子：
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影响因子：
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