NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis
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.
Authors
- Wendi Chen (ORCID: https://orcid.org/0000-0002-1554-8090)
- Yongzhi Cao (ORCID: https://orcid.org/0000-0001-9517-7332)
- Yunna Ning (ORCID: https://orcid.org/0009-0005-1174-0893)
- Huanxin Sun (ORCID: https://orcid.org/0000-0002-0298-6104)
- Gang Lü (ORCID: https://orcid.org/0000-0001-5921-1839)
- Guolong Wang
- Shuang Liu (ORCID: https://orcid.org/0000-0002-4372-8443)
- Ming Li (ORCID: https://orcid.org/0000-0001-8270-2070)
- Xin Liu (ORCID: https://orcid.org/0009-0004-7970-2327)
- Yueran Zhao (ORCID: https://orcid.org/0000-0002-2218-4918)
- Jing Zhang (ORCID: https://orcid.org/0009-0004-0512-3816)
- Yuxuan Shi (ORCID: https://orcid.org/0009-0000-8070-2982)
Institutions
- Shandong University (CN)
- Chinese University of Hong Kong (HK)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- European Journal of Pharmacology
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1016/j.ejphar.2024.177000
- Citations
- 2
- Primary Topic
- Bone Metabolism and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.47