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NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2024 Nov 15; Vol. 983, pp. 177000. Date of Electronic Publication: 2024 Sep 13. - Publication Year :
- 2024
-
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.<br />Competing Interests: Declaration of competing interest The authors declare no competing interests.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Female
RAW 264.7 Cells
Cell Differentiation drug effects
Molecular Docking Simulation
Osteoporosis drug therapy
Osteoporosis metabolism
Bone Resorption drug therapy
Bone Resorption pathology
Humans
Mice, Inbred C57BL
Osteoporosis, Postmenopausal drug therapy
Osteoporosis, Postmenopausal pathology
Osteoporosis, Postmenopausal metabolism
Disease Models, Animal
Ovariectomy
Osteoclasts drug effects
Osteoclasts metabolism
Osteogenesis drug effects
Cathepsin K metabolism
Cathepsin K genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 983
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39278311
- Full Text :
- https://doi.org/10.1016/j.ejphar.2024.177000