Casticin suppresses RANKL‑induced osteoclastogenesis and prevents ovariectomy‑induced bone loss by regulating the AKT/ERK and NF‑κB signaling pathways

Yang,Fan; Su,Yuangang; Liang,Jiamin; Wang,Keyi; Lian,Haoyu; Chen,Junchun; Xu,Jiake; Zhao,Jinmin; Liu,Qian

doi:10.3892/ijmm.2023.5246

Casticin suppresses RANKL‑induced osteoclastogenesis and prevents ovariectomy‑induced bone loss by regulating the AKT/ERK and NF‑κB signaling pathways

Authors:
- Fan Yang
- Yuangang Su
- Jiamin Liang
- Keyi Wang
- Haoyu Lian
- Junchun Chen
- Jiake Xu
- Jinmin Zhao
- Qian Liu
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Affiliations: Research Centre for Regenerative Medicine, Department of Orthopaedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, School of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia
Published online on: April 7, 2023 https://doi.org/10.3892/ijmm.2023.5246
Article Number: 43
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Postmenopausal osteoporosis is a systemic metabolic disease that chronically endangers public health and is typically characterized by low bone mineral density and marked bone fragility. The excessive bone resorption activity of osteoclasts is a major factor in the pathogenesis of osteoporosis; therefore, strategies aimed at inhibiting osteoclast activity may prevent bone decline and attenuate the process of osteoporosis. Casticin (Cas), a natural compound, has anti‑inflammatory and antitumor properties. However, the role of Cas in bone metabolism remains largely unclear. The present study found that the receptor activator of nuclear factor‑κΒ (NF‑κB) ligand‑induced osteoclast activation and differentiation were inhibited by Cas. Tartrate‑resistant acid phosphatase staining revealed that Cas inhibited osteoclast differentiation, and bone resorption pit assays demonstrated that Cas affected the function of osteoclasts. Cas significantly reduced the expression of osteoclast‑specific genes and related proteins, such as nuclear factor of activated T cells, cytoplasmic 1 and c‑Fos at the mRNA and protein level in a concentration‑dependent manner. Cas inhibited osteoclast formation by blocking the AKT/ERK and NF‑κB signaling pathways, according to the intracellular signaling analysis. The microcomputed tomography and tissue staining of tibiae from ovariectomized mice revealed that Cas prevented the bone loss induced by estrogen deficiency and reduced osteoclast activity in vivo. Collectively, these findings indicated that Cas may be used to prevent osteoporosis.

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