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We have previously identified the role of brain\u2010derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In our study, we investigated whether BDNF was possibly involved in MM cell\u2010induced osteolysis. We showed that BDNF was elevated in MM patients and the bone marrow plasma levels of BDNF positively correlated with extent of bone disease. In osteoclast formation assay, bone marrow plasma from patients with MM increased osteoclast formation and the effect was significantly blocked by neutralizing antibody to BDNF, suggesting a critical role for BDNF in osteoclast activation. Furthermore, the direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF, demonstrating that BDNF used TrkB for its effects on osteoclast. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein\u20101\u03b1 and receptor activator of nuclear factor\u2010\u03baB ligand, two major osteoclast stimulatory factors in MM. These results support an important role for BDNF in the development of myeloma bone disease.<\/jats:p>","DOI":"10.1002\/ijc.26059","type":"journal-article","created":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T16:18:16Z","timestamp":1299860296000},"page":"827-836","source":"Crossref","is-referenced-by-count":31,"title":["Brain\u2010derived neurotrophic factor is a potential osteoclast stimulating factor in multiple 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