ArticleJournal of orthopaedic surgery and research2025
Licochalcone D inhibits osteoclast differentiation and postmenopausal osteoporosis by inactivating the NF-κB signaling pathway.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
backgroundOsteoporosis is prevalent among postmenopausal women and is characterized by excessive bone resorption primarily mediated by osteoclasts. This study aimed to investigate the effects of the natural compound Licochalcone D (Lico D) on osteoclast differentiation and its therapeutic potential in ovariectomized (OVX) mouse models of osteoporosis.
methodsThe cytotoxicity of various doses of Lico D on mouse bone marrow-derived macrophages (BMMs) was evaluated using CCK-8 assays. The differentiation of BMMs into osteoclasts was induced by RANKL treatment, followed by exposure to Lico D at doses of 2, 4, and 8 µg/ml. Additionally, 10 µM BAY 11-7821 (an NF-κB inhibitor) was used to inhibit NF-κB signaling in RANKL-stimulated BMMs. TRAP staining was conducted to measure osteoblast cell number. Western blot analysis was performed to measure protein levels of osteoclast differentiation markers and NF-κB-related factors. RT-qPCR was performed to assess the mRNA levels of downstream genes in the NF-κB pathway. In animal experiments, OVX mice received intraperitoneal injections of Lico D at doses of 10 or 50 mg/kg. Subsequently, femurs were harvested for histopathological examination.
resultsLico D at doses of 2-8 µg/ml showed no significant cytotoxicity toward BMMs. In addition, Lico D inhibited RANKL-induced osteoclast formation and downregulated protein levels of osteoclast-specific genes (mmp9, ctsk, c-Fos and nfatc1). Moreover, Lico D suppressed the phosphorylation of NF-κB p65 and IκBα in RANKL-treated BMMs. Importantly, the suppressive effects of Lico D, especially at 8 µg/ml, on osteoclast cell number and osteoclast-specific markers were comparable to BAY 11-7821. Moreover, Lico D inhibited OVX-induced bone loss and restored dysregulated bone parameters in mice.
conclusionLico D inhibits RANKL-induced osteoclast differentiation and alleviates postmenopausal osteoporosis in mice by suppressing the NF-κB signaling pathway.
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