Korean J Physiol Pharmacol.  2025 Jul;29(4):443-454. 10.4196/kjpp.24.248.

Colla Carapacis et Plastri ameliorates postmenopausal osteoporosis and macrophage immunity by modulating the RANK/RANKL/OPG signaling pathway in ovariectomized rats

• Wan W
• Peng Z
• Luo J
• Luo J
• Zhu Y

• KMID: 2569539
• DOI: http://doi.org/10.4196/kjpp.24.248

Abstract

Postmenopausal osteoporosis (PMOP) is characterized by estrogen depletion, leading to skeletal demineralization and fractures. This study examines the impact of Colla Carapacis et Plastri (CCP) on PMOP in ovariectomized rats. Within this research, we replicated a rat model of PMOP through ovariectomy. The model rats were then intervened with low-dose CCP, high-dose CCP, and estrogen (positive control). The body weight was recorded, and the uterine index (UMI) was calculated. After intervention with CCP and the receptor activator of nuclear factor Κb (RANK) ligand (RANKL) inhibitor denosumab in PMOP rats, the bone microstructure, bone metabolism, macrophage M1/M2, and RANK/RANKL/Osteoprotegerin (OPG) signaling pathway-related factors were examined. These were conducted through hematoxylin and eosin staining, Biochemical kits and immunohistochemistry, respectively. The ovariectomized rat model was successfully established. Compared to the Sham group, rats in the Model group exhibited increased body weight, reduced UMI, and extensive damage to the microstructure of the femur. After intervention with CCP, the bone tissue microstructure of PMOP rats was repaired, as observed in increased levels of blood calcium level. Furthermore, CCP intervention led to reduced M1 macrophage levels (iNOS and CD86) and increased M2 macrophage levels (CD163 and CD206). Additionally, CCP treatment decreased RANK and RANKL expression levels and increased expression of OPG. The addition of denosumab further enhanced the effects of CCP. CCP can improve PMOP and regulate macrophage immunity in ovariectomized rats by modulating the RANK/RANKL/OPG signaling pathway.

Keyword

Colla Carapacis et Plastri; Macrophages; RANKL/RANK/OPG pathway; Postmenopausal osteoporosis