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.
Mol Med Rep. 2022 Jul;26(1). doi: 10.3892/mmr.2022.12741. Epub 2022 May 20.
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 , on RANKL‑induced osteoclastogenesis both and . 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 treatment with carnosol significantly attenuated ovariectomy‑induced bone loss in mice. In conclusion, the present study indicated that carnosol may suppress osteoclastogenesis both and 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.
骨稳态由破骨细胞介导的骨吸收和成骨细胞介导的骨形成维持。由于破骨细胞过度生成或成骨减少导致骨稳态破坏，会导致各种疾病，如绝经后骨质疏松症。核因子-κB 配体（RANKL）对 NF-κB 信号通路的刺激是破骨细胞生成所必需的。本研究旨在探讨姜酚，一种存在于 中的活性化合物，对 RANKL 诱导的破骨细胞生成的新作用。TRAP 染色显示，姜酚显著抑制骨髓单核细胞和 RAW264.7 细胞的破骨细胞分化。Western blot 结果表明，姜酚明显抑制破骨细胞生成相关基因的蛋白表达水平，包括组织蛋白酶 K、抗酒石酸酸性磷酸酶和 MMP-9，这可能抑制了破骨细胞的功能。此外，Western blot 和免疫荧光染色结果表明，姜酚显著抑制了 RANKL 诱导的 p65 磷酸化，并阻止其核转位，表明抑制了 NF-κB 信号通路。H&E 染色和 micro-CT 结果表明，姜酚治疗可显著减轻卵巢切除诱导的小鼠骨丢失。综上所述，本研究表明，姜酚可能通过抑制 NF-κB 信号通路的激活来抑制破骨细胞生成。因此，姜酚可能是治疗与破骨细胞相关疾病的一种有潜力的新型治疗候选药物。
