Cerium Oxide Nanoparticles Promote Osteoplastic Precursor Differentiation by Activating the Wnt Pathway

• Published in: Biological trace element research 2023-02, Vol.201 (2), p.865-873
• Main Authors: Luo, Junchao, Zhu, Senbo, Tong, Yu, Zhang, Yin, Li, Yong, Cao, Li, Kong, Mingxiang, Luo, Min, Bi, Qing, Zhang, Qiong
• Format: Article
• Language: English
• Subjects: Alizarin; Analysis; Animals; Biochemistry; Biomedical and Life Sciences; Biotechnology; Bone turnover; Cell Differentiation; Cerium; Cerium oxides; Collagen; Differentiation (biology); Extracellular matrix; Gene expression; Gene sequencing; Genes; Growth factors; Homeostasis; Life Sciences; Mesenchyme; Mice; Mineralization; Nanoparticles; Nuclear transport; Nucleotide sequence; Nutrition; Oncology; Osteoblastogenesis; Osteoblasts; Osteocalcin; Osteogenesis; Osteoprogenitor cells; PCR; Polymerase chain reaction; Precursors; Secretion; Stem cell transplantation; Stem cells; Toxicity; Transcription; Translocation; Wnt protein; Wnt Signaling Pathway; β-Catenin
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-022-03168-9

Osteoplastic precursors are critical for fracture repair and bone homeostasis maintenance. Cerium oxide nanoparticles (CeO 2 NPs) can promote the osteogenic differentiation of mesenchymal stem cells and secrete vascular endothelial growth factors. However, little is known about its role in precursor osteoblasts; therefore, we further investigated the effect and mechanism of CeO 2 NPs in precursor osteoblasts. Cell counting kit-8 analysis was utilized to detect the toxicity of CeO 2 NPs on MC3T3-E1 mouse osteogenic precursor cells. Then, alizarin red S staining was employed to assess the degree of extracellular matrix mineralization, and quantitative real-time polymerase chain reaction analysis was performed to measure the levels of osteogenesis-related genes. To identify differentially expressed genes, mRNA-sequencing was performed. Subsequently, GO and KEGG analyses were deployed to identify the major downstream pathways, whereas Western blot was used for verification. CeO 2 NPs significantly enhanced the ability of MC3T3-E1 precursor osteoblasts to enhance matrix mineralization and increased the expression of osteogenic genes such as runt-related transcription factor 2, collagen Iα1, and osteocalcin. Pathway analysis revealed that CeO 2 NPs enhanced the nuclear translocation of β-catenin and activated the Wnt pathway by promoting family with sequence similarity 53 member B/simplet expression, while Western blot analysis indicated the same results. After using a Wnt pathway inhibitor (KYA1797K), the simulative effect of CeO 2 NPs was abolished. This study revealed that CeO 2 NPs promoted MC3T3-E1 precursor osteoblast differentiation by activating the Wnt pathway.