Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo.
Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo.
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DOI：
10.1038/s41598-018-27461-7
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发表时间：
2018-06-15
影响因子：
4.6
通讯作者：
Okiji T
中科院分区：
文献类型：
--
作者：
Bakhit A;Kawashima N;Hashimoto K;Noda S;Nara K;Kuramoto M;Tazawa K;Okiji T
本研究探讨了雷奈酸锶（SrRn）（一种用于治疗骨质疏松症的药物）对克隆牙髓样细胞（小鼠牙乳头细胞；MDP）增殖和分化/矿化的影响和机制。它还确定了将 SrRn 局部应用于暴露的牙髓组织是否会促进体内矿化组织的形成。 MDP 在有或没有 SrRn 的情况下进行培养，并评估细胞增殖、牙本质/成骨细胞基因表达、矿化结节形成和 Akt 磷酸化。对大鼠上第一磨牙经 SrRn 处理的牙髓组织中矿化组织的形成进行了组织学评估。 SrRn 以剂量依赖性方式上调细胞增殖和 Alp（碱性磷酸酶）、Bsp（骨唾液蛋白）、Dmp（牙本质基质酸性磷蛋白）-1、Dspp（牙本质唾液酸磷蛋白）和 Oc（骨钙蛋白）的表达。 SrRn 也增强了矿化结核的形成。 NPS-2143 是一种钙敏感受体 (CaSR) 拮抗剂，和针对 CaSR 基因的 siRNA 可以阻断 SrRn 诱导的增殖、牙本质/成骨细胞基因表达和矿化结节形成。 SrRn 诱导 Akt 磷酸化，但这被 NPS-2143 阻断。将 SrRn 局部应用于暴露的大鼠磨牙牙髓可诱导骨牙本质样矿化组织的形成。我们的研究首次揭示，SrRn 在体外通过 CaSR 激活的 PI3K/Akt 信号传导促进 MDP 的增殖和牙向/成骨分化/矿化；矿化组织由体内牙髓形成。
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.
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影响因子：
5.8
作者：
Chattopadhyay, Naibedya;Quinn, Stephen J.;Brown, Edward M.
通讯作者：
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影响因子：
3.3
作者：
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DOI：
10.1006/bbrc.2000.3226
发表时间：
2000-08-28
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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