Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo

• Published in: Scientific reports Vol. 8; no. 1; p. 9224
• Main Authors: Bakhit, Alamuddin, Kawashima, Nobuyuki, Hashimoto, Kentaro, Noda, Sonoko, Nara, Keisuke, Kuramoto, Masashi, Tazawa, Kento, Okiji, Takashi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.06.2018; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 13; 13/106; 13/109; 13/89; 13/95; 38/39; 38/77; 631/136/142; 631/136/2091; 631/1647/2017/2003; 631/80/86/1999; 82/80; AKT protein; Alkaline phosphatase; Animals; Bone matrix; Bone sialoprotein; Calcification, Physiologic - drug effects; Calcium-sensing receptors; Cell growth; Cell proliferation; Dental pulp; Dental Pulp - cytology; Dental Pulp - metabolism; Dspp protein; Gene expression; Gene Expression Regulation - drug effects; Humanities and Social Sciences; Kinases; Mice; Mice, Inbred ICR; Mineralization; Molars; multidisciplinary; Nodules; Odontoblasts - cytology; Odontoblasts - metabolism; Odontogenesis - drug effects; Osteoblasts; Osteocalcin; Osteogenesis - drug effects; Osteoporosis; Papillae; Phosphorylation; Rats; Science; Science (multidisciplinary); siRNA; Strontium; Teeth; Thiophenes - pharmacology; Tissues; Topical application
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-27461-7

This study examined the effects and mechanisms of strontium ranelate (SrRn)—a drug used to treat osteoporosis—on the proliferation and differentiation/mineralization of cloned dental pulp-like cells (mouse dental papillae cells; MDPs). It also determined whether topical application of SrRn to exposed dental pulp tissue promotes the formation of mineralized tissue in vivo . The MDPs were cultured with or without SrRn, and cell proliferation, odonto-/osteoblastic gene expression, mineralized nodule formation, and Akt phosphorylation were evaluated. The formation of mineralized tissue in SrRn-treated pulp tissue in rat upper first molars was evaluated histologically. The SrRn up-regulated cell proliferation and expression of Alp (alkaline phosphatase) , Bsp (bone sialoprotein) , Dmp (dentin matrix acidic phosphoprotein)-1 , Dspp (dentin sialophosphoprotein) , and Oc (osteocalcin) in a dose-dependent manner. Mineralized nodule formation was also enhanced by SrRn. NPS-2143, a calcium-sensing receptor (CaSR) antagonist, and siRNA against the CaSR gene blocked SrRn-induced proliferation, odonto-/osteoblastic gene expression, and mineralized nodule formation. SrRn induced Akt phosphorylation, and this was blocked by NPS-2143. Topical application of SrRn to exposed rat molar pulps induced the formation of osteodentin-like mineralized tissue. Our study revealed for the first time that SrRn promotes proliferation and odonto-/osteogenic differentiation/mineralization of MDPs via PI3K/Akt signaling activated by CaSR in vitro ; mineralized tissue forms from the dental pulp in vivo .