Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis

Akane Inoue; Tamotsu Kiyoshima; Keigo Yoshizaki; Chihiro Nakatomi; Mitsushiro Nakatomi; Hayato Ohshima; Masashi Shin; Jing Gao; Kanji Tsuru; Koji Okabe; Ichiro Nakamura; Hiroaki Honda; Miho Matsuda; Ichiro Takahashi; Eijiro Jimi

doi:10.1016/j.bone.2021.116210

Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis

Bone. 2022 Jan:154:116210. doi: 10.1016/j.bone.2021.116210. Epub 2021 Sep 28.

Authors

Akane Inoue¹, Tamotsu Kiyoshima², Keigo Yoshizaki³, Chihiro Nakatomi⁴, Mitsushiro Nakatomi⁵, Hayato Ohshima⁶, Masashi Shin⁷, Jing Gao⁸, Kanji Tsuru⁹, Koji Okabe¹⁰, Ichiro Nakamura¹¹, Hiroaki Honda¹², Miho Matsuda⁸, Ichiro Takahashi³, Eijiro Jimi¹³

Affiliations

¹ Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth and Development, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
² Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
³ Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth and Development, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁴ Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
⁵ Department of Human, Information and Life Sciences, School of Health Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
⁶ Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
⁷ Department of Physiological Sciences and Molecular Biology, Fukuoka Dental College, 2-5-1 Tamura, Sawara-ku, Fukuoka 814-0175, Japan; Oral Medicine Center, Fukuoka Dental College, 2-5-1 Tamura, Sawara-ku, Fukuoka 814-0175, Japan.
⁸ Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁹ Section of Bioengineering, Fukuoka Dental College, 2-5-1 Tamura, Sawara-ku, Fukuoka 814-0175, Japan.
¹⁰ Department of Physiological Sciences and Molecular Biology, Fukuoka Dental College, 2-5-1 Tamura, Sawara-ku, Fukuoka 814-0175, Japan.
¹¹ Department of Rehabilitation, Yugawara Hospital, Japan Community Health Care Organization, 2-21-6 Chuo, Yugawara, Ashigara-shimo, Kanagawa 259-0396, Japan.
¹² Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Institute of Laboratory Animals, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
¹³ Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Oral Health/Brain Health/Total Health Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: ejimi@dent.kyushu-u.ac.jp.

PMID: 34592494
DOI: 10.1016/j.bone.2021.116210

Abstract

Amelogenesis consists of secretory, transition, maturation, and post-maturation stages, and the morphological changes of ameloblasts at each stage are closely related to their function. p130 Crk-associated substrate (Cas) is a scaffold protein that modulates essential cellular processes, including cell adhesion, cytoskeletal changes, and polarization. The expression of p130Cas was observed from the secretory stage to the maturation stage in ameloblasts. Epithelial cell-specific p130Cas-deficient (p130Cas^Δepi-) mice exhibited enamel hypomineralization with chalk-like white mandibular incisors in young mice and attrition in aged mouse molars. A micro-computed tomography analysis and Vickers micro-hardness testing showed thinner enamel, lower enamel mineral density and hardness in p130Cas^Δepi- mice in comparison to p130Cas^flox/flox mice. Scanning electron microscopy, and an energy dispersive X-ray spectroscopy analysis indicated the disturbance of the enamel rod structure and lower Ca and P contents in p130Cas^Δepi- mice, respectively. The disorganized arrangement of ameloblasts, especially in the maturation stage, was observed in p130Cas^Δepi- mice. Furthermore, expression levels of enamel matrix proteins, such as amelogenin and ameloblastin in the secretory stage, and functional markers, such as alkaline phosphatase and iron accumulation, and Na⁺/Ca²⁺+K⁺-exchanger in the maturation stage were reduced in p130Cas^Δepi- mice. These findings suggest that p130Cas plays important roles in amelogenesis (197 words).

Keywords: Ameloblasts; Biomineralizaion; Cell polarity; Crk-associated substrate protein; Dental enamel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ameloblasts / metabolism
Amelogenesis*
Animals
Crk-Associated Substrate Protein / metabolism*
Dental Enamel Proteins* / metabolism
Epithelial Cells / metabolism
Mice
X-Ray Microtomography

Substances

Bcar1 protein, mouse
Crk-Associated Substrate Protein
Dental Enamel Proteins