Wang Haoyu, Qian Jun
Department of Orthopaedics, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, No.100, Minjiang Avenue, Kecheng District, Quzhou City, 324000 Zhejiang Province China.
Cytotechnology. 2025 Jun;77(3):114. doi: 10.1007/s10616-025-00783-x. Epub 2025 Jun 4.
Picroside II (Pic II) has been used to treat many skeletal diseases. Postmenopausal osteoporosis (PMOP) is a serious skeletal disease that significantly threatens the health of postmenopausal women. We aimed to explore the roles and mechanisms of Pic II in PMOP. PMOP models were established by performing bilateral ovariectomy in rats and stimulating osteoblasts with HO. In vivo, micro-CT imaging, HE and MASSON staining were performed, and E, Ca/Cre, ALP, BGP, SOD, MDA, Fe and ROS levels were determined. In vitro, cell viability, apoptosis, mineralization, GSH and Fe levels were measured. Both animal and cell experiments detected the expressions of YY1, TGFβ1, SLC7A11, GPX4, RunX2 and BMP2 proteins. Moreover, PMOP cells were treated with N-Acetyl-L-cysteine (a ferroptosis inhibitor) to further explore the mechanisms of Pic II on PMOP. Pic II attenuated bone loss, improved femur pathological injury and increased collagen volume fraction for PMOP rats Furthermore, after Pic II treatment, PMOP rats exhibited decreased Ca/Cre, ALP, MDA, Fe and ROS levels, but increased E, BGP and SOD levels. In vitro, Pic II intervention elevated cell viability, GSH level and mineralization, suppressed apoptosis, and reduced ROS and Fe levels. Moreover, both animal and cell experiments observed that Pic II upregulated YY1, GPX4, SLC7A11, Runx2 and BMP2 expressions, but downregulated TGFβ1 expression. Importantly, Pic II exhibited similar effects to N-Acetyl-L-cysteine in PMOP cells. Pic II may regulate YY1/TGFβ1 axis by inhibiting osteoblast ferroptosis to alleviate PMOP, suggesting that Pic II may be a novel agent for PMOP treatment.
獐牙菜苦苷II（Pic II）已被用于治疗多种骨骼疾病。绝经后骨质疏松症（PMOP）是一种严重的骨骼疾病，严重威胁绝经后女性的健康。我们旨在探讨Pic II在PMOP中的作用及机制。通过对大鼠进行双侧卵巢切除术并用HO刺激成骨细胞来建立PMOP模型。在体内，进行了显微CT成像、HE和MASSON染色，并测定了E、Ca/Cre、ALP、BGP、SOD、MDA、Fe和ROS水平。在体外，测量了细胞活力、凋亡、矿化、GSH和Fe水平。动物和细胞实验均检测了YY1、TGFβ1、SLC7A11、GPX4、RunX2和BMP2蛋白的表达。此外，用N-乙酰-L-半胱氨酸（一种铁死亡抑制剂）处理PMOP细胞，以进一步探讨Pic II对PMOP的作用机制。Pic II减轻了PMOP大鼠的骨质流失，改善了股骨病理损伤，并增加了胶原体积分数。此外，Pic II治疗后，PMOP大鼠的Ca/Cre、ALP、MDA、Fe和ROS水平降低，但E、BGP和SOD水平升高。在体外，Pic II干预提高了细胞活力、GSH水平和矿化能力，抑制了凋亡，并降低了ROS和Fe水平。此外，动物和细胞实验均观察到Pic II上调了YY1、GPX4、SLC7A11、Runx2和BMP2的表达，但下调了TGFβ1的表达。重要的是，Pic II在PMOP细胞中表现出与N-乙酰-L-半胱氨酸相似的作用。Pic II可能通过抑制成骨细胞铁死亡来调节YY1/TGFβ1轴，从而减轻PMOP，这表明Pic II可能是一种治疗PMOP的新型药物。
