2. Academic Validation
  3. Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3

  • Biochem Pharmacol. 2024 Mar 11:222:116118. doi: 10.1016/j.bcp.2024.116118.
Jin Wu 1,  Xiang Li 2,  Hepeng Nie 3,  Yue Shen 1,  Zixiang Guo 1,  Catherine Huihan Chu 4,  Kunzhan Cai 1,  Chunbo Tang 5
Affiliations

Affiliations

  • 1 Department of Oral Implantology Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu Province 210029, China; Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China.
  • 2 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China; Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu Province 210029, China.
  • 3 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China; Department of General Dentistry Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu Province 210029, China.
  • 4 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China; Department of Orthodontics Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu Province 210029, China.
  • 5 Department of Oral Implantology Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu Province 210029, China; Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China. Electronic address: cbtang@njmu.edu.cn.
PMID: 38467376 DOI: 10.1016/j.bcp.2024.116118
Abstract

Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered MicroRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediatedBMSCosteogenic dysfunction and delayed bone regeneration in diabetes.

Keywords

Bone marrow mesenchymal stem cell; Osteogenic differentiation; Phytic acid; circEIF4B.

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