title: Topical application of lithium chloride on the pulp induces dentin regeneration.
abstract: We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration.
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Kazuya
authors: K
authors: Ishimoto
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Satoru
authors: S
authors: Hayano
authors: Department of Orthodontics, Okayama University Hospital, Okayama, Japan.
authors: Takeshi
authors: T
authors: Yanagita
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Hiroshi
authors: H
authors: Kurosaka
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Noriaki
authors: N
authors: Kawanabe
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Shinsuke
authors: S
authors: Itoh
authors: Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Mitsuaki
authors: M
authors: Ono
authors: Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Takuo
authors: T
authors: Kuboki
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Hiroshi
authors: H
authors: Kamioka
authors: Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical sciences, Okayama, Japan.
authors: Takashi
authors: T
authors: Yamashiro
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003782:Dental Pulp / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D003804:Dentin / Q000502:physiology*; D003810:Dentinogenesis / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D023421:Models, Animal; D008963:Molar / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D018021:Lithium Chloride; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein