ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation

被引：17
|
作者：
Nakata, Juri [1 ,2 ,3 ]
Akiba, Yosuke [2 ,4 ]
Nihara, Jun [1 ,2 ]
Thant, Lay [1 ,2 ,3 ]
Eguchi, Kaori [2 ,4 ]
Kato, Hiroko [2 ,5 ,6 ]
Izumi, Kenji [2 ,5 ]
Ohkura, Mariko [1 ,2 ]
Otake, Masanori [1 ,2 ]
Kakihara, Yoshito [2 ,3 ]
Saito, Isao [1 ,2 ]
Saeki, Makio [2 ,3 ]
机构：
[1] Niigata Univ, Fac Dent, Div Orthodont, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
[2] Niigata Univ, Grad Sch Med & Dent Sci, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
[3] Niigata Univ, Fac Dent, Div Dent Pharmacol, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
[4] Niigata Univ, Fac Dent, Div Bioprosthodont, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
[5] Niigata Univ, Fac Dent, Div Biomimet, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
[6] Niigata Univ, Fac Dent, Res Ctr Adv Oral Sci, Chuo Ku, 2-5274 Gakkocho Dori, Niigata 9518514, Japan
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 526卷 / 03期
关键词：
ROCK inhibitor; Osteoclastogenesis; Osteoblastosgenesis; Bone healing; GTP-BINDING PROTEIN; ENDOTHELIAL GROWTH-FACTOR; KINASE; FRACTURE; REPAIR; ORGANIZATION; RHOA;
D O I：
10.1016/j.bbrc.2020.03.033
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：547 / 552
页数：6
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