Research Paper|Volume 16, Issue 4|pp 3583—3595

Rutin promotes osteogenic differentiation of mesenchymal stem cells (MSCs) by increasing ECM deposition and inhibiting p53 expression

Dongyang Li^1,², Wanru Yin³, Chao Xu⁴, Yongmin Feng⁵, Xin Huang^6,⁷, Junfeng Hao^5,⁶, Chao Zhu¹

¹Department of Rheumatology and Immunology, The Third Affiliated Hospital of Naval Medical University, Shanghai 201805, China
²Department of Science and Education, Jinqiu Hospital of Liaoning Province, Shenyang, Liaoning 110016, China
³Department of Dermatology, Shenyang Medical University, Shenyang 110034, China
⁴Department of Digestive Ward, Shenyang Red Cross Society Hospital China, Shenyang 110013, China
⁵Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
⁶Department of General Practice Medicine, Shengjing Hospital of China Medical University, Shenyang 110022, China
⁷Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang 110000, China

* Equal contribution

Received: January 31, 2023Accepted: January 9, 2024Published: February 12, 2024

https://doi.org/10.18632/aging.205546

Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mesenchymal stem cells (MSCs) are an important source of cells for bone regeneration. Although the utilization of MSCs along with growth factors and scaffolds is a beneficial clinical approach for bone tissue engineering, there is need for improvement on the effectiveness of MSC osteogenesis and differentiation. Rutin is a natural flavonoid and a major component for cell proliferation and bone development. However, studies on the mechanism through which rutin regulates osteogenesis and MSC differentiation are limited. Therefore, this study aimed to investigate the effect and mechanisms of rutin on osteogenic differentiation of MSCs. MSCs were extracted from umbilical cords and treated with rutin, followed by the examination of osteogenesis-related markers. Rutin treatment promoted the differentiation of MSCs towards the osteogenic lineage rather than the adipogenic lineage and increased the expression of osteogenic markers. RNA sequencing and bioinformatic analysis indicated that rutin regulated p53, a key gene in regulating the osteogenic differentiation of MSCs. Additionally, cellular experiments showed that rutin-induced decrease in p53 expression increased the formation of extracellular matrix (ECM) by promoting p65 phosphorylation and caspase-3 cleavage. Conclusively, this study demonstrates the importance of rutin in osteogenesis and indicates that rutin possesses potential pharmaceutical application for bone regeneration and bone tissue engineering.