CDK5 inhibition promotes osteoblastic differentiation of MSCs and blocks the migration of osteosarcoma MG-63 cells

Hong Fu,Siyu Wang,Yali Yang,Ke Duan,Tailin Guo,Haoyu Zhao

doi:10.32604/biocell.2022.017435

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.

Highlights

CDK5 is a member of the cyclin-dependent kinase (CDK) family and shares 60% sequence identity to CDK1
DLC1 is a GTPase-activating protein (GAP) that can down-regulate the activation of Ras homolog family member A (RhoA) (Kim et al, 2007)
CDK5 inhibition promotes the osteoblastic differentiation by increasing the polymerization of F-actin which promotes the nuclear localization of Yesassociated Protein (YAP) and β-catenin, as well as the expression of RMRP RNA, Runx2 and ALP

Summary

Introduction

CDK5 is a member of the cyclin-dependent kinase (CDK) family and shares 60% sequence identity to CDK1. Unlike other CDKs, CDK5 is the only CDK that does not play a role in the cell cycle. It is expressed ubiquitously and mostly expressed in the brain (Tsai et al, 1993). Pak is a positive regulator for RAC family small GTPase 1, a kinase able to promote the polymerization of actin. CDK5 can be a negative regulator of Ras homolog family member A (RhoA). DLC1 is a GTPase-activating protein (GAP) that can down-regulate the activation of RhoA (Kim et al, 2007).

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Conclusion