川芎嗪基于miR-20b调控骨关节炎软骨下骨血管-成骨耦联的作用机制研究进展

Research progress on the mechanism of tetramethylpyrazine in regulating “vascular-osteogenic coupling” in osteoarthritis subchondral bone via miR-20b

关键词:  骨关节炎  软骨下骨  血管-成骨耦联  川芎嗪  微小RNA-20b

Key words:  osteoarthritis  subchondral bone  vascular-osteogenic coupling  tetramethylpyrazine  microRNA-20b

摘要:

骨关节炎软骨下骨“血管-成骨耦联”失衡是疾病进展的关键病理环节，涉及VEGF信号介导的血管生成亢进与骨形态发生蛋白2（BMP2）/Smad1信号调控的成骨分化失调。文章基于中医药“整体调节”理论，首次提出川芎嗪可能通过靶向微小RNA miR-20b，协同调控上述双信号轴，恢复软骨下骨稳态的创新假说。文中系统梳理证据表明，miR-20b可抑制表皮生长因子（VEGF）通路并激活BMP2/Smad1通路，而川芎嗪兼具有抑制血管生成、促进成骨及调节miRNA表达的多重药理活性。该假说为阐释中药“多靶点”干预复杂疾病提供新范式，并为骨关节炎的疾病修饰治疗提供潜在靶点与候选药物，未来需借助基因编辑动物模型、单细胞组学及靶向递送系统进一步验证其机制，推动中医药现代化与精准治疗融合发展。

Abstract:

The imbalance of"vascular-osteogenic coupling"in the subchondral bone is a pivotal pathological link in the progression of osteoarthritis (OA), involving hyperactivity of angiogenesis mediated by the vascular endothelial growth factor (VEGF) signaling pathway and dysregulation of osteogenic differentiation governed by the bone morphogenetic protein 2 (BMP2) /Smad1 signaling axis. Grounded in the "holistic regulation" theory of traditional Chinese medicine (TCM), this study proposes, for the first time, an innovative hypothesis that tetramethylpyrazine (TMP, ligustrazine) may restore subchondral bone homeostasis by targeting microRNA miR-20b to synergistically regulate the aforementioned dual signaling pathways. A systematic review of the evidence indicates that miR-20b can inhibit the VEGF pathway and activate the BMP2/Smad1 pathway, while TMP exhibits multiple pharmacological activities, including suppressing angiogenesis, promoting osteogenesis, and modulating miRNA expression. This hypothesis provides a novel paradigm for elucidating the "multi-target" intervention strategy of Chinese herbal medicine in complex diseases and offers potential therapeutic targets and a candidate drug for disease-modifying OA therapy. Future research should employ gene-edited animal models, single-cell omics, and targeted delivery systems to further validate this mechanism, thereby fostering the integrated development of TCM modernization and precision medicine.