Sphingosine-1-phosphate receptor 2 agonist induces bone formation in rat apicoectomy and alveolar bone defect model

鞘氨醇-1-磷酸受体 2 激动剂在大鼠根尖切除术和牙槽骨缺损模型中诱导骨形成

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作者:Etsuko Matsuzaki, Haruna Hirose, Seishiro Fujimasa, Shohei Yoshimoto, Tsukasa Yanagi, Kazuma Matsumoto, Misaki Nikaido, Masahiko Minakami, Noriyoshi Matsumoto, Hisashi Anan

Conclusion

In the rat apicoectomy and alveolar bone defect model, therapeutic agents targeting S1PR2 agonist are effective against osteogenesis.

Methods

Sphingosine-1-phosphate receptor (S1PR) 1/S1PR3 agonists, S1PR2 agonists, and their signal-related agents were intraperitoneally administered to mice. Using the mRNA collected from the tibial bone, the expression of osteoblast differentiation markers was evaluated by real-time reverse-transcriptase quantitative polymerase chain reaction. An apicoectomy and alveolar bone defect model was established on the mesial root of the rat mandibular first molar. Bone formation parameters were measured by micro-computed tomography analysis 3 weeks after the procedure.

Purpose

Sphingosine-1-phosphate (S1P) is a lipid mediator that exerts its physiological functions in vivo through receptors. In the bone, S1P induces osteoblast differentiation. Here, we investigated the effects of S1P receptor agonists on the expression of osteoblast differentiation markers locally in the bone. Then, a rat apicoectomy and alveolar bone defect model was established to extend S1P applications to endodontics, and the effect of local administration of S1P receptor agonist on postoperative bone formation was examined. Materials and

Results

Intraperitoneal administration of S1PR2 agonist significantly increased the mRNA expression of osteoblast differentiation markers, including alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin, in the local tibial bone of mice. The S1PR2/Rho-associated coiled-coil forming kinase (ROCK) signaling was thought to be involved in the upregulated mRNA expression of ALP, OPN, and BSP. In the rat apical defects, bone formation parameters significantly increased following local administration of S1PR2 agonist.

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