Matsuzaki Etsuko, Hirose Haruna, Fujimasa Seishiro, Yoshimoto Shohei, Yanagi Tsukasa, Matsumoto Kazuma, Nikaido Misaki, Minakami Masahiko, Matsumoto Noriyoshi, Anan Hisashi
Section of Operative Dentistry and Endodontology, Department of Odontology, Fukuoka Dental College, Fukuoka, Japan.
Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan.
J Dent Sci. 2022 Apr;17(2):787-794. doi: 10.1016/j.jds.2021.10.004. Epub 2021 Oct 19.
BACKGROUND/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.
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.
Intraperitoneal administration of S1PR2 agonist significantly increased the mRNA expression of osteoblast differentiation markers, including alkaline phosphatase (, osteopontin (, bone sialoprotein (), 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 , , and . In the rat apical defects, bone formation parameters significantly increased following local administration of S1PR2 agonist.
In the rat apicoectomy and alveolar bone defect model, therapeutic agents targeting S1PR2 agonist are effective against osteogenesis.
背景/目的：1-磷酸鞘氨醇（S1P）是一种脂质介质，可通过受体在体内发挥其生理功能。在骨骼中，S1P可诱导成骨细胞分化。在此，我们研究了S1P受体激动剂对骨骼局部成骨细胞分化标志物表达的影响。然后，建立大鼠根尖切除术和牙槽骨缺损模型，将S1P的应用扩展到牙髓病学领域，并检测局部给予S1P受体激动剂对术后骨形成的影响。
将1-磷酸鞘氨醇受体（S1PR）1/S1PR3激动剂、S1PR2激动剂及其信号相关试剂腹腔注射给小鼠。使用从胫骨收集的mRNA，通过实时逆转录定量聚合酶链反应评估成骨细胞分化标志物的表达。在大鼠下颌第一磨牙的近中根上建立根尖切除术和牙槽骨缺损模型。术后3周通过微计算机断层扫描分析测量骨形成参数。
腹腔注射S1PR2激动剂可显著增加小鼠局部胫骨中成骨细胞分化标志物的mRNA表达，包括碱性磷酸酶、骨桥蛋白、骨唾液蛋白和骨钙素。S1PR2/ Rho相关卷曲螺旋形成激酶（ROCK）信号通路被认为参与了、和mRNA表达的上调。在大鼠根尖缺损中，局部给予S1PR2激动剂后骨形成参数显著增加。
在大鼠根尖切除术和牙槽骨缺损模型中，靶向S1PR2激动剂的治疗药物对成骨有效。
