{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:23:37Z","timestamp":1791113017644,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p>Osteolytic bone diseases are a prominent feature of multiple myeloma (MM), resulting from aberrant osteoclastic bone resorption that is uncoupled from osteoblastic bone formation. Myeloma stimulates osteoclastogenesis, which is largely dependent on an increase in receptor activator of NF\u2010\u03baB ligand (RANKL) and a decrease in osteoprotegerin (OPG) within the bone marrow milieu. Recently, brain\u2010derived neurotrophic factor (BDNF) was identified as a MM\u2010derived factor that correlates with increased RANKL levels and contributes to osteolytic bone destruction in myeloma patients. Because tyrosine receptor kinase B (TrkB), the receptor of BDNF, is abundantly expressed in osteoblasts, we sought to evaluate the role of BDNF\/TrkB in myeloma\u2013osteoblast interactions and the effect of this pathway on the RANKL\/OPG ratio and osteoclastogenesis. Coculture systems constructed with noncontact transwells revealed that, <jats:italic>in vitro<\/jats:italic>, MM\u2010derived BDNF increased RANKL and decreased OPG production in osteoblasts in a time\u2010 and dose\u2010dependent manner. These effects were completely abolished by a specific small interfering RNA for TrkB. BDNF regulates RANKL\/OPG expression in osteoblasts through the TrkB\/ERK pathway. To investigate the biological effects of BDNF on myeloma <jats:italic>in vivo<\/jats:italic>, a SCID\u2010RPMI8226 mice model was constructed using lentiviral short hairpin RNA\u2010transfected RPMI8226 cells. In this system, stable knockdown of BDNF in MM cells significantly restored the RANKL\/OPG homostasis, inhibited osteolytic bone destruction and reduced angiogenesis and tumor burden. Our studies provide further support for the potential osteoclastogenic effects of BDNF, which mediates stroma\u2013myeloma interactions to disrupt the balance of RANKL\/OPG expression, ultimately increasing osteoclastogenesis in MM.<\/jats:p>","DOI":"10.1002\/ijc.28116","type":"journal-article","created":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T17:39:51Z","timestamp":1361295591000},"page":"1074-1084","source":"Crossref","is-referenced-by-count":21,"title":["Gene silencing of the BDNF\/TrkB axis in multiple myeloma blocks bone destruction and tumor burden in vitro and in vivo"],"prefix":"10.1002","volume":"133","author":[{"given":"Li\u2010Sha","family":"Ai","sequence":"first","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang\u2010Bo","family":"Chu","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Qin","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22403"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-007-9485-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2003.10.005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1687"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040116"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3883"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/16852"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1260"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8697"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0380"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201394498"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03417.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0148"},{"key":"e_1_2_7_16_1","first-page":"5438","article-title":"Receptor activator of nuclear factor\u2010kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo","volume":"63","author":"Farrugia AN","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_17_1","first-page":"275","article-title":"Lack of receptor activator of nuclear factor\u2010kB ligand (RANKL) expression and functional production by human multiple myeloma cells","volume":"90","author":"Giuliani N","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.08.004"},{"key":"e_1_2_7_19_1","first-page":"237","article-title":"BDNF function and intracellular signaling in neurons","volume":"25","author":"Numakawa T","year":"2010","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1086"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.2001.00331.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.02.025"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-11-23"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3096"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5490-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2006.02.018"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.3027"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2010.01515.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26059"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046287"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65287-X"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.12.009"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0532-0"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3527"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.01.027"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050207"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1311567"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05775.2000"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.04.026"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.09.010"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/08977190410001723308"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1089\/104303403322168037"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009690"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1121"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2258"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-1992"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.671"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28116","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:55:57Z","timestamp":1696352157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,8]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1002\/ijc.28116"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28116","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,8]]}}}