title: Promotion of dentin regeneration via CCN3 modulation on Notch and BMP signaling pathways.
abstract: Dentin regeneration remains a great challenge in clinic. Dental pulp stem cells (DPSCs) actively contribute to dentinogenesis, which is orchestrated by a spectrum of signaling factors. However, the exact mechanism underlying the reparative dentin regeneration process is largely unknown and the application of DPSCs in the repair of dentin defect is thus limited. Here, using a rat reparative dentin regeneration model, we observed that DPSCs underwent a proliferation phase followed by a differentiation phase after dental injury. A transient elevation of nephroblastoma overexpressed (NOV, or CCN3) expression correlated with this progressive dental tissue restoration process. Further studies revealed that over-expression of CCN3 promoted human DPSCs proliferation via activation of Notch. Moreover, using cocultured cells (DPSCs/CCN3 and DPSCs) in vitro and the cocultured cells-poly (lactic-co-glycolic acid) (PLGA) scaffold complex in vivo, we demonstrated that CCN3 was capable of promoting mineralization in a non-cell autonomous manner through promoting secretion of BMP2. CCN3 can promote dentinogenesis by coordinating proliferation and odontoblastic differentiation of DPSCs via modulating Notch and BMP2 signaling pathways and CCN3 is a promising therapeutic target in dentin tissue engineering.
authors.affiliation: Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Maxillofacial and Head-Neck Surgery, Daping Hospital, Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China. Electronic address: tanyinghui@outlook.com.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology; D003804:Dentin / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D055514:Nephroblastoma Overexpressed Protein / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D055514:Nephroblastoma Overexpressed Protein; D051880:Receptors, Notch; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Bone morphogenetic protein (BMP); Dental pulp stem cell (DPSCs); Dentin regeneration; Nephroblastoma overexpressed (NOV, or CCN3); Notch; Poly lactic-co-glycolic acid (PLGA) scaffold