Bone formation ability of Gli1+ cells in the periodontal ligament after tooth extraction

Saki Fujii; Hiroaki Takebe; Toshihide Mizoguchi; Hiroaki Nakamura; Tsuyoshi Shimo; Akihiro Hosoya

doi:10.1016/j.bone.2023.116786

Bone formation ability of Gli1⁺ cells in the periodontal ligament after tooth extraction

Bone. 2023 Aug:173:116786. doi: 10.1016/j.bone.2023.116786. Epub 2023 May 8.

Authors

Saki Fujii¹, Hiroaki Takebe², Toshihide Mizoguchi³, Hiroaki Nakamura⁴, Tsuyoshi Shimo⁵, Akihiro Hosoya⁶

Affiliations

¹ Division of Histology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan; Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
² Division of Histology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
³ Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.
⁴ Department of Oral Anatomy, Matsumoto Dental University, Nagano, Japan.
⁵ Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
⁶ Division of Histology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. Electronic address: hosoya@hoku-iryo-u.ac.jp.

PMID: 37164217
DOI: 10.1016/j.bone.2023.116786

Abstract

During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1⁺-PDL cells after tooth extraction was analyzed using Gli1-Cre^ERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. After the final administration of tamoxifen to iGli1/Tomato mice, Gli1/Tomato⁺ cells were rarely detected in the PDL. One day after the tooth extraction, although inflammatory cells appeared in the tooth socket, Periostin⁺ PDL-like tissues having a few Gli1/Tomato⁺ cells remained near the alveolar bone. Three days after the extraction, the number of Gli1/Tomato⁺ cells increased as evidenced by numerous PCNA⁺ cells in the socket. Some of these Gli1/Tomato⁺ cells expressed BMP4 and Phosphorylated (P)-Smad1/5/8. After seven days, the Osteopontin⁺ bone matrix was formed in the tooth socket apart from the alveolar bone. Many Gli1/Tomato⁺ osteoblasts that were positive for Runx2⁺ were arranged on the surface of the newly formed bone matrix. In the absence of Gli1⁺-PDL cells in Gli1-Cre^ERT2/Rosa26-loxP-stop-loxP-tdDTA (iGli1/DTA) mice, the amount of newly formed bone matrix was significantly reduced in the tooth socket. Therefore, these results collectively suggest that Gli1⁺-PDL cells differentiate into osteoblasts to form the bone matrix in the tooth socket; thus, this differentiation might be regulated, at least in part, by bone morphogenetic protein (BMP) signaling.

Keywords: BMP signaling; Cell-lineage analysis; Mesenchymal stem cell; Osteoblast differentiation; Periodontal ligament.

Publication types

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

MeSH terms

Animals
Hedgehog Proteins
Mice
Osteogenesis*
Periodontal Ligament*
Tooth Extraction
Zinc Finger Protein GLI1

Substances

Zinc Finger Protein GLI1
Hedgehog Proteins