2. Academic Validation
  3. NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis

NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis

  • Eur J Pharmacol. 2024 Nov 15:983:177000. doi: 10.1016/j.ejphar.2024.177000.
Xin Liu 1,  Shuang Liu 1,  Huanxin Sun 1,  Jing Zhang 1,  Ming Li 1,  Yuxuan Shi 1,  Guolong Wang 1,  Wendi Chen 1,  Yongzhi Cao 1,  Gang Lu 2,  Yunna Ning 3,  Yueran Zhao 4
Affiliations

Affiliations

  • 1 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.
  • 2 CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • 3 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. Electronic address: yunna_ning@163.com.
  • 4 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. Electronic address: yrzhao@sdu.edu.cn.
PMID: 39278311 DOI: 10.1016/j.ejphar.2024.177000
Abstract

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.

Keywords

Cathepsin K; Inflammation; NVP-BHG712; Osteoclast differentiation; Osteoporosis.

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