title: Histochemical Examination on Periodontal Tissues of Klotho-Deficient Mice Fed With Phosphate-Insufficient Diet.
abstract: To elucidate which of elevated serum concentration of inorganic phosphate (Pi) or disrupted signaling linked to αklotho/fibroblast growth factor 23 (FGF23) is a predominant regulator for senescence-related degeneration seen in αKlotho-deficient mice, we have examined histological alteration of the periodontal tissues in the mandibular interalveolar septum of αKlotho-deficient mice fed with Pi-insufficient diet. We prepared six groups of mice: wild-type, kl/kl, and αKlotho-/-mice with normal diet or low-Pi diet. As a consequence, kl/klnorPiand αKlotho-/-norPimice showed the same abnormalities in periodontal tissues: intensely stained areas with hematoxylin in the interalveolar septum, dispersed localization of alkaline phosphatase-positive osteoblasts and tartrate-resistant acid phosphatase-reactive osteoclasts, and accumulation of dentin matrix protein 1 in the osteocytic lacunae. Although kl/kllowPimice improved these histological abnormalities, αKlotho-/- lowPimice failed to normalize those. Gene expression of αKlotho was shown to be increased in kl/kllowPispecimens. It seems likely that histological abnormalities of kl/kl mice have been improved by the rescued expression of αKlotho, rather than low concentration of serum Pi. Thus, the histological malformation in periodontal tissues in αKlotho-deficient mice appears to be due to not only increased concentration of Pi but also disrupted αklotho/FGF23 signaling.
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.|Department of Orthodontics (KH, JI), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hikone
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Tsuchiya
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hongo
authors.affiliation: Department of Applied Prosthodontics, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan (MS).
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomomaya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Division of Biochemistry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan (KO).
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Haraguchi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Dr. Mário Gatti Municipal Hospital, Campinas, Brazil (PHLF).
authors.forename: Paulo Henrique Luiz
authors.initials: PH
authors.lastname: de Freitas
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, School of Stomatology, Shandong University, Jinan, China (ML).
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthodontics (KH, JI), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Iida
authors.affiliation: Department of Developmental Biology of Hard Tissue (KH, TH, ET, HH, TY, AK, MH, NA), Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D000818:Animals; D004032:Diet; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006651:Histocytochemistry; D000090265:Klotho Proteins; D008297:Male; D008334:Mandible / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D010513:Periodontal Ligament / Q000378:metabolism; D010519:Periodontium / Q000378:metabolism*; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*
chemical_list: C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: DMP-1; osteopontin; periodontal tissue; phosphate; αKlotho-deficient mice