title: Bone morphogenetic protein-9 effectively induces osteo/odontoblastic differentiation of the reversibly immortalized stem cells of dental apical papilla.
abstract: Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing bone formation. Here, we investigate whether BMP9 can effectively induce odontogenic differentiation of the stem cells from mouse apical papilla (SCAPs). Using a reversible immortalization system expressing SV40 T flanked with Cre/loxP sites, we demonstrate that the SCAPs can be immortalized, resulting in immortalized SCAPs (iSCAPs) that express mesenchymal stem cell markers. BMP9 upregulates Runx2, Sox9, and PPARγ2 and odontoblastic markers, and induces alkaline phosphatase activity and matrix mineralization in the iSCAPs. Cre-mediated removal of SV40 T antigen decreases iSCAP proliferation. The in vivo stem cell implantation studies indicate that iSCAPs can differentiate into bone, cartilage, and, to lesser extent, adipocytes upon BMP9 stimulation. Our results demonstrate that the conditionally iSCAPs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages, including osteo/odontoblastic differentiation. Thus, the reversibly iSCAPs may serve as an important tool to study SCAP biology and SCAP translational use in tooth engineering. Further, BMP9 may be explored as a novel and efficacious factor for odontogenic regeneration.
authors: 1 Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and The Affiliated Hospital of Stomatology of Chongqing Medical University , Chongqing, China .
authors: Jinhua
authors: J
authors: Wang
authors: Hongmei
authors: H
authors: Zhang
authors: Wenwen
authors: W
authors: Zhang
authors: Enyi
authors: E
authors: Huang
authors: Ning
authors: N
authors: Wang
authors: Ningning
authors: N
authors: Wu
authors: Sheng
authors: S
authors: Wen
authors: Xian
authors: X
authors: Chen
authors: Zhan
authors: Z
authors: Liao
authors: Fang
authors: F
authors: Deng
authors: Liangjun
authors: L
authors: Yin
authors: Junhui
authors: J
authors: Zhang
authors: Qian
authors: Q
authors: Zhang
authors: Zhengjian
authors: Z
authors: Yan
authors: Wei
authors: W
authors: Liu
authors: Zhonglin
authors: Z
authors: Zhang
authors: Jixing
authors: J
authors: Ye
authors: Youlin
authors: Y
authors: Deng
authors: Hue H
authors: HH
authors: Luu
authors: Rex C
authors: RC
authors: Haydon
authors: Tong-Chuan
authors: TC
authors: He
authors: Feng
authors: F
authors: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D003771:Dental Papilla / Q000166:cytology / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D055427:Growth Differentiation Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009804:Odontoblasts / Q000378:metabolism; D009805:Odontogenesis; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism
chemical_list: C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2