{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T15:50:17Z","timestamp":1765209017588,"version":"3.46.0"},"reference-count":35,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Center Program","award":["RS-2022-NR070844"],"award-info":[{"award-number":["RS-2022-NR070844"]}]},{"name":"Basic Science Research Program","award":["RS-2022-NR068998"],"award-info":[{"award-number":["RS-2022-NR068998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Osteoporosis is a major global health challenge, causing millions of fragility fractures each year and imposing an escalating socioeconomic burden worldwide. Despite advances with antiresorptive and anabolic therapies, substantial residual fracture risk persists, and targeting aging biology may yield disease modifying benefits beyond current standards of care. Senescent cells secrete senescence-associated secretory phenotype (SASP) factors, which impair osteoblast differentiation and contribute to bone loss. We investigated foretinib, a quinoline-based multi-tyrosine kinase inhibitor, as a potential anti-aging agent in osteoblast lineage cells. Foretinib inhibited doxorubicin-induced senescence in osteoblast progenitors via the p53\/p21 and p16 pathways and reduced the expression of osteogenesis-inhibiting SASP factors, including CCL2, interleukin (IL)-1\u03b1, IL-1\u03b2, and IL-6. As a result, foretinib restored the impaired osteogenic differentiation of aged osteoblasts to near-normal levels in vitro. In ovariectomized, estrogen-deficient mice, foretinib significantly reduced trabecular and cortical bone loss by enhancing in vivo osteoblast differentiation, as shown by histological analysis and micro-computed tomography of femoral bone. These results suggest that foretinib alleviates osteoblast senescence and enhances osteogenic differentiation, supporting its promise as a therapeutic candidate for postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3390\/cells14241945","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Foretinib Alleviates Osteoblast Senescence and Protects Against Bone Loss in Ovariectomized Mice by Promoting Osteoblast Differentiation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-7805","authenticated-orcid":false,"given":"Jiin","family":"Oh","sequence":"first","affiliation":[{"name":"Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jueun","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eok-Cheon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Senotherapy-Based Metabolic Disease Control Research Center, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Ryoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Senotherapy-Based Metabolic Disease Control Research Center, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunil","family":"Ha","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7503-9725","authenticated-orcid":false,"given":"Taesoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyunghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daewon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kumari, R., and Jat, P. 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