Carnosol inhibits osteoclastogenesis <em>in vivo</em> and <em>in vitro</em> by blocking the RANKL‑induced NF‑κB signaling pathway

Cai,Pan; Yan,Shichang; Lu,Yan; Zhou,Xiaoxiao; Wang,Xiuhui; Wang,Minghui; Yin,Zhifeng

doi:10.3892/mmr.2022.12741

Carnosol inhibits osteoclastogenesis in vivo and in vitro by blocking the RANKL‑induced NF‑κB signaling pathway

Authors:
- Pan Cai
- Shichang Yan
- Yan Lu
- Xiaoxiao Zhou
- Xiuhui Wang
- Minghui Wang
- Zhifeng Yin
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Affiliations: Department of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, Department of Orthopedics, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu 210019, P.R. China, Department of Laboratory Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200941, P.R. China
Published online on: May 20, 2022 https://doi.org/10.3892/mmr.2022.12741
Article Number: 225
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast‑mediated bone formation. Disruption of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis results in various disorders, such as postmenopausal osteoporosis. Receptor activator of NF‑κB ligand (RANKL) stimulation of the NF‑κB signaling pathway is essential in osteoclastogenesis. The aim of the present study was to investigate the novel effects of carnosol, an active compound found in Rosmarinus officinalis, on RANKL‑induced osteoclastogenesis both in vitro and in vivo. TRAP staining showed that carnosol significantly inhibited osteoclasts differentiation of bone marrow monocytes and RAW264.7 cells. Western blot results showed that the protein expression levels of osteoclastogenesis‑associated genes, including cathepsin K, tartrate‑resistant acid phosphatase and MMP‑9, were markedly inhibited by carnosol, which may have suppressed osteoclast function. Furthermore, western blot and immunofluorescent staining results revealed that carnosol markedly suppressed the phosphorylation of p65 induced by RANKL and blocked its nuclear translocation, indicating the suppression of NF‑κB signaling pathway. H&E staining and micro‑CT results showed that in vivo treatment with carnosol significantly attenuated ovariectomy‑induced bone loss in mice. In conclusion, the present study indicated that carnosol may suppress osteoclastogenesis both in vivo and in vitro by inhibiting the activation of the NF‑κB signaling pathway. Carnosol may therefore be a potential novel therapeutic candidate for the clinical treatment of osteoclast‑related disorders.

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