title: The transcription factor mohawk homeobox regulates homeostasis of the periodontal ligament.
abstract: The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well known. We report that mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and expression remained at similar levels at 12 months. In Mkx-/-mice, age-dependent expansion of the PDL at the maxillary first molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx-/-mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx+/+mice. PDL cells lost their shape in Mkx-/-mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx-/-PDL revealed an increase in osteogenic gene expression and no change in PDL- and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkx-overexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis.
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.|Maxillofacial Orthognathics, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koda
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tempei
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.|JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakamichi
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kayama
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Maxillofacial Orthognathics, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan asahara.syst@tmd.ac.jp.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-161, La Jolla, CA 92037, USA.
authors.forename: Hiroshi
authors.identifier: 0000-0002-5215-8745
authors.initials: H
authors.lastname: Asahara
mesh_terms: D016301:Alveolar Bone Loss / Q000235:genetics / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics; D010513:Periodontal Ligament / Q000502:physiology*
chemical_list: C000619309:Col1a2 protein, mouse; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D018398:Homeodomain Proteins; C510657:mohawk protein, mouse
keywords: Collagen; Mohawk; Mouse; Osteogenic change; PDL homeostasis