Department of Orthopedic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.
Chem Biol Drug Des. 2024 Sep;104(3):e14625. doi: 10.1111/cbdd.14625.
Arctigenin (Ar) is a promising therapeutic candidate for postmenopausal osteoporosis (PMOP). This study explores its mechanism by examining its effects on adipogenesis and osteogenesis in ovariectomized (OVX) rats. In vitro, Ar effectively suppressed the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from OVX rats, reducing lipid droplet formation and downregulating proteins associated with lipid synthesis. In vivo, Ar treatment significantly reduced bone loss, inhibited adipocyte development, improved lipid metabolism, and promoted bone formation in OVX rats. Mechanistically, Ar inhibited the phosphorylation of Mitogen-Activated Protein Kinase 1 (MEK1), downregulated Peroxisome Proliferator-Activated Receptor gamma (PPARγ), promoted the accumulation of β-catenin in the nucleus, and prevented the direct binding of PPARγ to β-catenin in BMSCs. This regulation of the PPARγ/Wnt signaling axis underlies its dual role in inhibiting adipogenesis and promoting osteogenesis. Notably, co-treatment with rosiglitazone (RGZ) reversed the effects of Ar on adipogenesis and osteogenesis without affecting MEK1 inhibition. These findings offer valuable insights into arctigenin's potential as a therapeutic strategy for PMOP by modulating MEK1 signaling and regulating the PPARγ/Wnt axis.
牛蒡子苷元（Ar）是治疗绝经后骨质疏松症（PMOP）的一种很有前途的治疗候选药物。本研究通过观察其对去卵巢（OVX）大鼠脂肪生成和成骨的影响来探讨其作用机制。在体外，Ar 有效抑制了来自 OVX 大鼠的骨髓间充质干细胞（BMSCs）的脂肪生成分化，减少了脂滴形成，并下调了与脂质合成相关的蛋白。在体内，Ar 治疗显著减少了骨丢失，抑制了脂肪细胞发育，改善了脂质代谢，并促进了 OVX 大鼠的骨形成。在机制上，Ar 抑制丝裂原活化蛋白激酶 1（MEK1）的磷酸化，下调过氧化物酶体增殖物激活受体γ（PPARγ），促进β-连环蛋白在细胞核中的积累，并防止 PPARγ与 BMSCs 中β-连环蛋白的直接结合。这种对 PPARγ/Wnt 信号通路的调节是其在抑制脂肪生成和促进成骨作用中的双重作用的基础。值得注意的是，与罗格列酮（RGZ）共同处理逆转了 Ar 对脂肪生成和成骨的作用，而不影响 MEK1 抑制。这些发现为通过调节 MEK1 信号和调节 PPARγ/Wnt 轴来调节 MEK1 信号和调节 PPARγ/Wnt 轴提供了有价值的见解，为 PMOP 的治疗策略提供了有价值的见解。
