2. Academic Validation
  3. PDCD4 Negatively Regulated Osteogenic Differentiation and Bone Defect Repair of Mesenchymal Stem Cells Through GSK-3β/β-Catenin Pathway

PDCD4 Negatively Regulated Osteogenic Differentiation and Bone Defect Repair of Mesenchymal Stem Cells Through GSK-3β/β-Catenin Pathway

  • Stem Cells Dev. 2021 Aug 15;30(16):806-815. doi: 10.1089/scd.2021.0041.
Yang Jiang 1 2 3,  Shuo Li 1 4,  Qian Zhou 1 5,  Shenghou Liu 6,  Xiaoli Liu 1 2 3,  Juan Xiao 1 2 3,  Wen Jiang 1 7,  Yaqi Xu 1 2 3,  Dexiao Kong 1 2 3,  Fang Wang 7,  Fengtao Wei 8,  Chengyun Zheng 1 2 3
Affiliations

Affiliations

  • 1 Hematology Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 Institute of Biotherapy for Hematological Malignancies, Shandong University, Jinan, China.
  • 3 Shandong University-Karolinska Institute Collaborative Laboratory for Stem Cell Research, Shandong University, Jinan, China.
  • 4 Hematology Department, Binzhou Medical University Hospital, Binzhou, China.
  • 5 Hematology Department, Linyi Central Hospital, Yishui, China.
  • 6 Department of Joint Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 7 Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 8 Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
PMID: 34088227 DOI: 10.1089/scd.2021.0041
Abstract

Mesenchymal stem cells (MSCs) have been shown to be involved in bone injury repair. Programmed cell death 4 (PDCD4) is not only a tumor suppressor gene but also plays roles in the regulation of MSC function. The aim of the study was to uncover PDCD4 potential regulatory roles and mechanisms in the osteogenic differentiation and bone defect repair of MSCs. shRNA technique was used to knock down PDCD4 expression in umbilical cord-derived mesenchymal stem cells (shPDCD4-UCMSCs). Their phenotype was characterized by flow cytometry and the differentiation potential was verified. We found that PDCD4 knockdown did not affect the surface molecule expression of UCMSCs, but significantly enhanced their osteogenic differentiation and osteogenesis-related molecule expression. Mechanistically, glycogen synthase kinase-3β (GSK-3β) phosphorylation and β-catenin expression were significantly increased in shPDCD4-UCMSCs during the osteogenic differentiation process. The β-catenin Inhibitor PNU-74654 reversed shPDCD4-increased osteogenesis and osteogenesis-related molecule expression. The results of animal experiments showed that shPDCD4-UCMSCs markedly improved the defect healing in rabbits. Our findings suggest that PDCD4 acts as a negative regulator of MSC osteogenic differentiation through GSK-3β/β-catenin pathway. Targeting PDCD4 may be a way to improve MSC-mediated therapeutic effects on bone injury.

Keywords

GSK-3β/β-catenin; MSC; PDCD4; migration; osteogenesis.

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