{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:05:43Z","timestamp":1779692743719,"version":"3.53.1"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Excessive bone resorption by osteoclasts causes pathological bone loss in diseases such as osteoporosis. 7-Deacetoxy-7-oxogedunin (CG-1), a limonoid isolated from Carapa guianensis (Meliaceae), exhibits various biological activities. Here, we examined the anti-osteoclastogenic effect of CG-1 and its underlying mechanism in receptor activator of NF-\u03baB ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells. CG-1 inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and decreased the expression of osteoclastogenesis-related genes. When CG-1 was added to the culture during the first 3 days of the 5-day-osteoclastogenesis period, the expression levels of the osteoclastogenesis-related genes (Nfatc1, Acp5, Src, Ctsk, and Mmp9) were decreased, as was observed when CG-1 was added continuously for 5 days. Furthermore, CG-1 lowered RANKL-induced Akt phosphorylation, which is similar to the results seen with the PI3K inhibitor, LY294002. Moreover, CG-1 and LY294002 suppressed the RANKL-induced expression of NFATc1, the master transcription factor for regulating terminal differentiation into osteoclasts. These results suggest that CG-1 attenuated RANKL-induced osteoclastogenesis by inhibiting the PI3K\/Akt-NFATc1 axis during the early stage of osteoclast differentiation. Thus, CG-1 has the potential to suppress osteoclast-mediated bone resorption.<\/jats:p>","DOI":"10.3390\/cells15100854","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limonoid 7-Deacetoxy-7-oxogedunin (CG-1) Attenuates RANKL-Induced Osteoclastogenesis via Inhibiting PI3K\/Akt-NFATc1 Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Atsushi","family":"Koike","sequence":"first","affiliation":[{"name":"Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-0769","authenticated-orcid":false,"given":"Ko","family":"Fujimori","sequence":"additional","affiliation":[{"name":"Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-022-00190-4","article-title":"Mechanical regulation of bone remodeling","volume":"10","author":"Wang","year":"2022","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The global prevalence of osteoporosis in the world: A comprehensive systematic review and meta-analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J. 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