{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:51:25Z","timestamp":1778881885071,"version":"3.51.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,10,15]],"date-time":"2013-10-15T00:00:00Z","timestamp":1381795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003639","name":"Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["A111345"],"award-info":[{"award-number":["A111345"]}],"id":[{"id":"10.13039\/501100003639","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007431","name":"Basic Science Research Program through the National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["NRF-2013R1A1A2A10005515"],"award-info":[{"award-number":["NRF-2013R1A1A2A10005515"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>GNF-2, a tyrosine kinase inhibitor, was developed to overcome imatinib-resistant mutations found in CML patients. Osteoclasts are the principal bone-resorbing cells that are responsible for bone diseases, such as osteoporosis, tumor-induced osteolysis, and metastatic cancers. In this study, we investigated the effect of GNF-2 on osteoclast development induced by RANKL and M-CSF. We found that GNF-2 inhibited osteoclast differentiation from BMMs. GNF-2 suppressed RANKL-induced NF-\u03baB transcriptional activity and the induction of c-Fos and NFATc1, which are two key transcription factors in osteoclastogenesis. We also observed that GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts. In agreement with its in vitro effects, GNF-2 reduced osteoclast number and bone loss in a mouse model of LPS-induced bone destruction. Taken together, our data reveal that GNF-2 possesses anti-bone-resorptive properties, suggesting that GNF-2 may have therapeutic value for the treatment of bone-destructive disorders that can occur as a result of excessive osteoclastic bone resorption.<\/jats:p>","DOI":"10.1189\/jlb.0713356","type":"journal-article","created":{"date-parts":[[2013,10,16]],"date-time":"2013-10-16T04:32:50Z","timestamp":1381897970000},"page":"337-345","source":"Crossref","is-referenced-by-count":16,"title":["The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity"],"prefix":"10.1093","volume":"95","author":[{"given":"Hyun-Ju","family":"Kim","sequence":"first","affiliation":[{"name":"Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Kyungpook National University School of Medicine , Daegu, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye-Jin","family":"Yoon","sequence":"additional","affiliation":[{"name":"Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Kyungpook National University School of Medicine , Daegu, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Je-Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Kyungpook National University School of Medicine , Daegu, South Korea"},{"name":"Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine , Daegu, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyungpook National University School of Medicine , Daegu, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Kyungpook National University School of Medicine , Daegu, South Korea"},{"name":"Department of Orthopedic Surgery, Kyungpook National University School of Medicine , Daegu, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,10,15]]},"reference":[{"key":"2023032711075673000_","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/36593","article-title":"A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function","volume":"390","author":"Anderson","year":"1997","journal-title":"Nature"},{"key":"2023032711075673000_","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"2023032711075673000_","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1084\/jem.186.12.2075","article-title":"TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor","volume":"186","author":"Wong","year":"1997","journal-title":"J. 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