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Hlaing, Ei Ei Hsu Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Ishihara, Yoshihito Department of Orthodontics, Okayama University Hospital Kaken ID researchmap
Wang, Ziyi Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Odagaki, Naoya Department of Orthodontics, Okayama University Hospital
Kamioka, Hiroshi Department of Orthodontics and Dentofacial Orthopedics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kaken ID publons
Abstract
Human periodontal ligament (hPDL) fibroblasts are thought to receive mechanical stress (MS) produced by orthodontic tooth movement, thereby regulating alveolar bone remodeling. However, the role of intracellular calcium ([Ca2+]i)‐based mechanotransduction is not fully understood. We explored the MS‐induced [Ca2+]i responses both in isolated hPDL fibroblasts and in intact hPDL tissue and investigated its possible role in alveolar bone remodeling. hPDL fibroblasts were obtained from healthy donors' premolars that had been extracted for orthodontic reasons. The oscillatory [Ca2+]i activity induced by static compressive force was measured by a live‐cell Ca2+ imaging system and evaluated by several feature extraction method. The spatial pattern of cell‐cell communication was investigated by Moran's I , an index of spatial autocorrelation and the gap junction (GJ) inhibitor. The Ca2+‐transporting ionophore A23187 was used to further investigate the role of [Ca2+]i up‐regulation in hPDL cell behavior. hPDL fibroblasts displayed autonomous [Ca2+]i responses. Compressive MS activated this autonomous responsive behavior with an increased percentage of responsive cells both in vitro and ex vivo . The integration, variance, maximum amplitude, waveform length, and index J in the [Ca2+]i responses were also significantly increased, whereas the mean power frequency was attenuated in response to MS. The increased Moran's I after MS indicated that MS might affect the pattern of cell‐cell communication via GJs. Similar to the findings of MS‐mediated regulation, the A23187‐mediated [Ca2+]i uptake resulted in the up‐regulation of receptor activator of NF‐κB ligand (Rankl) and Sost along with increased sclerostin immunoreactivity, suggesting that [Ca2+]i signaling networks may be involved in bone remodeling. In addition, A23187‐treated hPDL fibroblasts also showed the suppression of osteogenic differentiation and mineralization. Our findings suggest that augmented MS‐mediated [Ca2+]i oscillations in hPDL fibroblasts enhance the production and release of bone regulatory signals via Rankl/Osteoprotegerin and the canonical Wnt/β‐catenin pathway as an early process in tooth movement–initiated alveolar bone remodeling.—Ei Hsu Hlaing, E., Ishihara, Y., Wang, Z., Odagaki, N., Kamioka, H. Role of intracellular Ca2+‐based mechanotransduction of human periodontal ligament fibroblasts. FASEB J. 33, 10409–10424 (2019).
Keywords
hPDL
intracellular calcium
SOST/sclerostin
Rankl/Opg
bone remodeling
Published Date
2019-09
Publication Title
FASEB Journal
Volume
volume33
Issue
issue9
Publisher
Federation of American Society of Experimental Biology
Start Page
10409
End Page
10424
ISSN
08926638
NCID
AA1066874X
Content Type
Journal Article
language
英語
File Version
publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1096/fj.201900484R
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
助成番号
17H04413
19H03859