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

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/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/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.