ROCK抑制剂通过促进破骨细胞和成骨细胞分化来增强骨愈合。
ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation.
作者信息
Nakata Juri, Akiba Yosuke, Nihara Jun, Thant Lay, Eguchi Kaori, Kato Hiroko, Izumi Kenji, Ohkura Mariko, Otake Masanori, Kakihara Yoshito, Saito Isao, Saeki Makio
机构信息
Division of Orthodontics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan; Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Division of Bio-Prosthodontics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
出版信息
Biochem Biophys Res Commun. 2020 Jun 4;526(3):547-552. doi: 10.1016/j.bbrc.2020.03.033. Epub 2020 Mar 17.
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.
破骨细胞和成骨细胞对于正常的骨骼发育、重塑以及骨折愈合至关重要。在本研究中，我们寻找能够增强骨代谢周转以促进骨愈合的化合物。首先，我们通过使用小鼠破骨前体细胞RAW264.7筛选了一个包含378种化合物的化学文库，以鉴定促进破骨细胞分化的化合物。我们发现两种ROCK（Rho相关卷曲螺旋激酶）抑制剂，HA-1077（法舒地尔）和Y-27632，可增强破骨细胞生成。随后，我们确定这两种化合物还能增加MC3T3-E1细胞的成骨细胞分化。最后，我们的体内实验表明，局部施用ROCK抑制剂可加速大鼠颅骨缺损的骨愈合。
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