Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.
Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.
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DOI：
10.1002/bies.201600104
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发表时间：
2016-08
期刊：
影响因子：
4
通讯作者：
Aoki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Sugamori, Yasutaka;Mise-Omata, Setsuko;Maeda, Chizuko;Aoki, Shigeki;Tabata, Yasuhiko;Murali, Ramachandran;Yasuda, Hisataka;Udagawa, Nobuyuki;Suzuki, Hiroshi;Honma, Masashi;Aoki, Kazuhiro
关键词：
已知W 9和OP 3 - 4均可结合NF-κB配体受体激活剂（RANKL），抑制破骨细胞生成。最近，这两种肽显示刺激成骨细胞分化，然而，这些肽的活性的机制仍有待澄清。原代成骨细胞培养显示，雷帕霉素（一种mTORC 1抑制剂，最近被证明是骨形成的重要丝氨酸/苏氨酸激酶）抑制肽诱导的碱性磷酸酶活性。此外，这两种肽促进Akt和S6 K1的磷酸化，Akt和S6 K1分别是mTORC 1的上游分子和mTORC 1的效应分子。在体内颅骨缺损模型中，W 9和OP 3 - 4以相似的程度加速BMP-2诱导的骨形成，这通过使用未脱钙切片的荧光图像的组织形态计量学分析得到证实。我们的数据表明，这些RANKL结合肽可以刺激mTORC 1活性，这可能在RANKL结合肽加速BMP-2诱导的骨再生中发挥作用。
Both W9 and OP3‐4 were known to bind the receptor activator of NF‐κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide‐induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3‐4 accelerated BMP‐2‐induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL‐binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP‐2‐induced bone regeneration by the RANKL‐binding peptides.
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用核因子 - κB配体（RANKL）结合肽的受体激活剂治疗的小鼠的皮质骨刺激骨形成，该肽具有破骨构成抑制活性。
DOI：
10.1074/jbc.m112.426080
发表时间：
2013-02-22
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Furuya Y;Inagaki A;Khan M;Mori K;Penninger JM;Nakamura M;Udagawa N;Aoki K;Ohya K;Uchida K;Yasuda H
通讯作者：
Yasuda H
影响因子：
4
作者：
Komori, T
通讯作者：
Komori, T
影响因子：
4.8
作者：
Cheng, X;Kinosaki, M;Murali, R
通讯作者：
Murali, R
影响因子：
6.2
作者：
Aoki, Shigeki;Honma, Masashi;Suzuki, Hiroshi
通讯作者：
Suzuki, Hiroshi
影响因子：
--
作者：
Saito, Hiroaki;Kojima, Takefumi;Aoki, Kazuhiro
通讯作者：
Aoki, Kazuhiro