Lotfi Mohammad-Sadegh, Rassouli Fatemeh B
Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Stem Cells Int. 2025 Sep 12;2025:8019494. doi: 10.1155/sci/8019494. eCollection 2025.
Bone defects pose significant clinical challenges, necessitating the development of innovative strategies to effectively restore damaged bone and recover normal function. Mesenchymal stem cells (MSCs) have emerged as a promising tool for bone regeneration due to their accessibility from various sources, ease of isolation and expansion, and intrinsic ability to differentiate into osteogenic lineages with minimal ethical concerns. However, successful bone repair using MSCs requires the incorporation of biocompatible osteoinductive agents, preferably derived from natural sources. Natural polyphenols, particularly flavonoids, exhibit potent pharmaceutical properties that modulate MSC fate toward osteogenic differentiation. These secondary metabolites promote osteogenesis by interacting with key bone regulatory signaling pathways, including bone morphogenetic protein 2 (BMP2)/SMAD, wingless-related integration site (Wnt)/β-catenin, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and mitogen-activated protein kinase (MAPK). Beyond their osteoinductive capacity, flavonoids possess anti-inflammatory, antibacterial, and pro-angiogenic effects, which synergistically enhance bone formation both in vitro and in vivo, thereby amplifying their therapeutic potential. This review synthesizes current insights into the interaction between MSCs and natural flavonoids, detailing the molecular mechanisms driving their synergistic effects. It also highlights recent advancements in nanoformulation-based delivery systems aimed at addressing challenges like poor solubility and bioavailability. Although preclinical data strongly support the bone-protective properties of these agents, their clinical translation remains forthcoming. Future studies must focus on optimizing delivery methods, ensuring long-term safety, and rigorously validating therapeutic efficacy across various bone disorders.
骨缺损带来了重大的临床挑战，因此需要开发创新策略来有效修复受损骨骼并恢复正常功能。间充质干细胞（MSCs）已成为一种有前景的骨再生工具，因为它们可以从多种来源获取，易于分离和扩增，并且具有内在的分化为成骨谱系的能力，同时伦理问题较少。然而，使用MSCs成功进行骨修复需要加入生物相容性的骨诱导剂，最好是来源于天然物质。天然多酚，特别是黄酮类化合物，具有强大的药学特性，可调节MSCs向成骨分化的命运。这些次生代谢产物通过与关键的骨调节信号通路相互作用来促进骨生成，这些信号通路包括骨形态发生蛋白2（BMP2）/SMAD、无翅相关整合位点（Wnt）/β-连环蛋白、活化B细胞核因子κB轻链增强子（NF-κB）和丝裂原活化蛋白激酶（MAPK）。除了骨诱导能力外，黄酮类化合物还具有抗炎、抗菌和促血管生成作用，在体外和体内协同增强骨形成，从而扩大其治疗潜力。本综述综合了目前对MSCs与天然黄酮类化合物相互作用的见解，详细阐述了驱动它们协同效应的分子机制。它还强调了基于纳米制剂的递送系统的最新进展，旨在解决诸如溶解性差和生物利用度低等挑战。尽管临床前数据有力地支持了这些药物的骨保护特性，但它们的临床转化仍有待实现。未来的研究必须专注于优化递送方法，确保长期安全性，并严格验证针对各种骨疾病的治疗效果。
