Department of Endocrinology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, No.336 Dongfeng South Road, Zhuhui District, Hengyang, 421001, Hunan, China.
Hum Cell. 2022 Jul;35(4):1045-1059. doi: 10.1007/s13577-022-00704-6. Epub 2022 May 11.
Osteoporosis (OP) is a frequent orthopedic disease characterized by pain, fractures and deformities. Glucocorticoids are the most common cause of secondary osteoporosis. Here, we aim to explore the function and mechanism of STK11 in glucocorticoid (GC)-induced OP. Human mesenchymal stromal cells (hMSCs) were differentiated under osteogenic or adipogenic culture medium. An in-vitro OP model was induced by dexamethasone (DEX). The viability, differentiation, apoptosis, and ROS level were evaluated for investigating the functions of SKT11 on hMSCs. The SIRT1 inhibitor EX-527, PGC1α inhibitor SR-18292, and AMPK activator metformin were administered into hMSCs for confirming the mechanism of SKT11. Our results showed that STK11 was down-regulated in OP tissues, as well as DEX-treated hMSCs. Overexpressing STK11 attenuated DEX-mediated inhibition of osteogenic differentiation and heightened the activation of the AMPK/SIRT1/PGC1α pathway, whereas STK11 knockdown exerted opposite effects. Inhibiting SIRT1 or PGC1α repressed the promotive effect of STK11 on osteogenic differentiation of hMSCs, while activation of AMPK abated the inhibitory effect of STK11 knockdown on osteogenic differentiation of hMSCs. In conclusion, this study revealed that overexpressing STK11 dampened GC-induced OP by activating the AMPK/SIRT1/PGC1α axis.
骨质疏松症（OP）是一种常见的骨科疾病，其特征是疼痛、骨折和畸形。糖皮质激素是继发性骨质疏松症最常见的原因。在这里，我们旨在探索 STK11 在糖皮质激素（GC）诱导的 OP 中的作用和机制。人间充质基质细胞（hMSC）在成骨或成脂培养基中分化。用地塞米松（DEX）诱导体外 OP 模型。评估 SKT11 对 hMSC 的活力、分化、凋亡和 ROS 水平，以研究 SKT11 在 hMSC 中的功能。将 SIRT1 抑制剂 EX-527、PGC1α 抑制剂 SR-18292 和 AMPK 激活剂二甲双胍施用于 hMSC 以确认 SKT11 的机制。我们的结果表明，STK11 在 OP 组织和 DEX 处理的 hMSC 中下调。过表达 STK11 减弱了 DEX 介导的成骨分化抑制作用，并增强了 AMPK/SIRT1/PGC1α 通路的激活，而 STK11 敲低则产生相反的效果。抑制 SIRT1 或 PGC1α 抑制了 STK11 对 hMSC 成骨分化的促进作用，而 AMPK 的激活减轻了 STK11 敲低对 hMSC 成骨分化的抑制作用。总之，这项研究表明，过表达 STK11 通过激活 AMPK/SIRT1/PGC1α 轴来减轻 GC 诱导的 OP。
