CK1ε drives osteogenic differentiation of bone marrow mesenchymal stem cells via activating Wnt/β-catenin pathway

• Published in: Aging (Albany, NY.) Vol. 15; no. 19; pp. 10193 - 10212
• Main Authors: Yu, Zhentang, Jiang, Xijia, Yin, Jianjian, Han, Lei, Xiong, Chengwei, Huo, Zhennan, Xu, Jie, Shang, Jingjing, Xi, Kun, Nong, Luming, Huang, Yong, Zhou, Xindie
• Format: Journal Article
• Language: English
• Published: Impact Journals 15-10-2023
• Subjects: Research Paper
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.205067

The treatment of bone defects is a difficult problem in orthopedics. At present, the treatment mainly relies on autologous or allogeneic bone transplantation, which may lead to some complications such as foreign body rejection, local infection, pain, or numbness at the bone donor site. Local injection of conservative therapy to treat bone defects is one of the research hotspots at present. Bone marrow mesenchymal stem cells (BMSCs) can self-renew, significantly proliferate, and differentiate into various types of cells. Although it has been reported that CK1ε could mediate the Wnt/β-catenin pathway, leading to the development of the diseases, whether CK1ε plays a role in bone regeneration through the Wnt/β-catenin pathway has rarely been reported. The purpose of this study was to investigate whether CK1ε was involved in the osteogenic differentiation (OD) of BMSCs through the Wnt/β-catenin pathway and explore the mechanism. We used quantitative reverse transcription-polymerase chain reaction (qRT-qPCR), Western blots, immunofluorescence, alkaline phosphatase, and alizarin red staining to detect the effect of CK1ε on the OD of BMSCs and the Wnt/β-catenin signaling pathway. CK1ε was highly expressed in BMSCs with OD, and our study further demonstrated that CK1ε might promote the OD of BMSCs by activating DLV2 phosphorylation, initiating Wnt signaling downstream, and activating β-catenin nuclear transfer. In addition, by locally injecting a CK1ε-carrying adeno-associated virus (AAV5- CK1ε) into a femoral condyle defect rat model, the overexpression of CK1ε significantly promoted bone repair. Our data show that CK1ε was involved in the regulation of OD by mediating Wnt/β-catenin. This may provide a new strategy for the treatment of bone defects.