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

• Published in: Bone (New York, N.Y.) Vol. 173; p. 116786
• Main Authors: Fujii, Saki, Takebe, Hiroaki, Mizoguchi, Toshihide, Nakamura, Hiroaki, Shimo, Tsuyoshi, Hosoya, Akihiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2023
• Subjects: Animals; BMP signaling; Cell-lineage analysis; Hedgehog Proteins; Mesenchymal stem cell; Mice; Osteoblast differentiation; Osteogenesis; Periodontal Ligament; Tooth Extraction; Zinc Finger Protein GLI1; Mesenchymal stem cell; Cell-lineage analysis; BMP signaling; Periodontal ligament; Osteoblast differentiation
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2023.116786

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-CreERT2/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-CreERT2/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.
•Gli1+-periodontal ligament (PDL) cells remained in the tooth socket.•After tooth extraction, Gli1+ cells in the PDL differentiated into osteoblasts.•BMP signaling might relate the osteoblast differentiation of Gli1+-PDL cells.