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Arcyriaflavin A as a Potential Therapeutic Agent for Osteoporosis

Year: 2025
Type: dissertation
Abstract: In this study, Arcyriaflavin A (ArcyA), a natural compound derived from the marine organism Eudistoma sp., was investigated as a potential therapeutic approach for osteoporosis. To evaluate the inhibitory effects of ArcyA on osteoclast differentiation and function, molecular analyses, cellular functional assays, and in vivo experiments in mouse models were performed on both mouse and human cells. ArcyA significantly reduced the number of TRAP-positive cells at concentrations that were non-toxic to bone marrow-derived macrophages (BMMs). These inhibitory effects were also confirmed in human osteoclasts derived from peripheral blood mononuclear cells (PBMCs). At the molecular level, ArcyA treatment downregulated key genes associated with osteoclast differentiation (NFATc1, cFos, TNFRSF11α), fusion and survival (DCSTAMP, ATP6v0d2), as well as resorption (CTSK, MMP9, Integrin β3, ACP5). Western blot analyses confirmed these results at the protein level, particularly for NFATc1, cFos, CTSK, and Integrin β3. Moreover, in vitro functional assays indicated that the ArcyA reduced bone-resorptive activity. Furthermore, the results suggested that IκB may serve as a potential target for the inhibitory effect of ArcyA. In vivo experiments using an ovariectomy (OVX)-induced osteoporosis model demonstrated that ArcyA treatment significantly attenuated bone loss. Treated mice exhibited an increased bone volume-to-tissue volume (BV/TV) ratio in a dose-dependent manner. In conclusion, ArcyA shows promising therapeutic potential for the treatment of osteoporosis by inhibiting osteoclastogenesis and bone resorption.
DOI: 10.48565/bonndoc-658
Author: Zhu, Mengbo
Institution: University of Bonn
Language: English
Open Access status: green
OpenAlex ID: W7083670658
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