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CDK5 inhibition promotes osteoblastic differentiation of MSCs and blocks the migration of osteosarcoma MG-63 cells
Authors:HONG FU  HAOYU ZHAO  YALI YANG  SIYU WANG  KE DUAN  TAILIN GUO
Affiliation:1.College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China2 Provincial Laboratory of Orthopaedic Engineering, Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
Abstract:CDK5 belongs to the cyclin-dependent kinase family. CDK5 is multifunctional and plays an important role in neural differentiation. However, the role of CDK5 in osteoblastic differentiation remains unclear. The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation. It was found that, CDK5 inhibition promoted the expression of Runx2, ALP, OCN and OPN of MSCs and the mineralization of MC-3T3E1 cells and MSCs. CDK5 inhibition enhanced the development of F-actin, nuclear localization of β-catenin and YAP, as well as the expression of RMRP RNA. When F-actin was suppressed by Blebbistatin, the nuclear localization of YAP and β-catenin, and expression of RMRP RNA as well as Runx2 and ALP were decreased. These indicate Seliciclib promotes osteoblastic differentiation mainly by F-actin. Moreover, Seliciclib also suppressed the migration of MG-63, suggesting a potential application for Seliciclib in bone defect repair and inhibition of the migration of osteosarcoma cells after osteosarcoma surgical resection.
Keywords:F-actin  YAP  Beta-catenin  Nuclear localization  MSC differentiation
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