NVP-BHG712 通过调节破骨细胞生成来缓解卵巢切除诱导的骨质疏松症。
NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis.
机构信息
State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.
CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
出版信息
Eur J Pharmacol. 2024 Nov 15;983:177000. doi: 10.1016/j.ejphar.2024.177000. Epub 2024 Sep 13.
Postmenopausal osteoporosis (PMOP) is closely related to the pathogenesis of osteoclasts, with the Cathepsin K (CTSK) protein playing a crucial role. Our study aimed to screen small molecule compounds targeting CTSK and evaluate their impact on PMOP. Through molecular docking, we identified NVP-BHG712 as significantly inhibiting osteoclast differentiation and bone resorption. NVP-BHG712 also effectively suppressed CTSK activity and exhibited strong binding affinity to CTSK protein. Furthermore, NVP-BHG712 regulated the expression of inflammatory factors and modulated the balance between M1 and M2 macrophage polarization. In the mouse model of ovariectomy-induced osteoporosis, NVP-BHG712 rescued bone loss by inhibiting excessive osteoclast activation. These findings suggest that NVP-BHG712 may be a promising treatment for pathological osteoporosis by alleviating osteoclast function.
绝经后骨质疏松症（PMOP）与破骨细胞的发病机制密切相关，组织蛋白酶 K（CTSK）蛋白起着关键作用。我们的研究旨在筛选针对 CTSK 的小分子化合物，并评估它们对 PMOP 的影响。通过分子对接，我们确定 NVP-BHG712 可显著抑制破骨细胞分化和骨吸收。NVP-BHG712 还能有效抑制 CTSK 活性，并与 CTSK 蛋白具有很强的结合亲和力。此外，NVP-BHG712 调节炎症因子的表达，并调节 M1 和 M2 巨噬细胞极化之间的平衡。在卵巢切除诱导的骨质疏松症小鼠模型中，NVP-BHG712 通过抑制过度的破骨细胞激活来挽救骨丢失。这些发现表明，NVP-BHG712 可能通过缓解破骨细胞功能成为治疗病理性骨质疏松症的一种有前途的方法。
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