ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation
ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation
复制标题
DOI：
10.1016/j.bbrc.2020.03.033
复制
发表时间：
2020-06-04
影响因子：
3.1
通讯作者：
Saeki, Makio
中科院分区：
文献类型：
--
作者：
Nakata, Juri;Akiba, Yosuke;Saeki, Makio
破骨细胞和成骨细胞对于骨骼的正常发育和重塑以及骨折的恢复都是必不可少的。在本研究中，我们寻找能够促进骨代谢的化合物，以促进骨愈合。首先，我们通过使用小鼠破骨前细胞RAW264.7来筛选包含378种化合物的化学库，以识别促进破骨细胞分化的化合物。我们发现两种ROCK(Rho相关的螺旋卷曲激酶)抑制剂，HA-1077(法舒地尔)和Y-27632，促进破骨细胞的形成。随后，我们发现这两个化合物也能促进MC3T3-E1细胞向成骨细胞分化。最后，我们的活体实验表明，局部应用ROCK抑制剂加速了大鼠颅骨缺损的骨愈合。(C)2020 Elsevier Inc.保留所有权利。
Osteoclast and osteoblast are essential for proper bone development and remodeling as well as recovery of bone fracture. In this study, we seek chemical compounds that enhance turnover of bone metabolism for promoting bone healing. First, we screen a chemical library which includes 378 compounds by using murine pre-osteoclastic RAW264.7 cells to identify compounds that promote osteoclastic differentiation. We find that two ROCK (Rho-associated coiled-coil kinase) inhibitors, HA-1077 (Fasudil) and Y-27632, enhance osteoclastogenesis. Subsequently, we identify that these two compounds also increase osteoblastic differentiation of MC3T3-E1 cells. Finally, our in vivo experiment shows that the local administration of ROCK inhibitors accelerate the bone healing of the rat calvarial defect. (C) 2020 Elsevier Inc. All rights reserved.