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We investigated the role of the OPG\/RANKL\/RANK network in the pathogenesis of skeletal metastasis in neuroblastoma. Four different neuroblastoma cell lines (NB100, CHP212, SH\u2010SY5Y, SJ\u2010NK\u2010P) showed a large amount of OPG and RANKL transcripts. Soluble RANKL was detectable in all cell lines, but poor release of OPG was observed. SH\u2010SY5Y showed the lowest OPG\u2010to\u2010RANKL ratio and promoted osteoclastic differentiation of FLG29.1 and peripheral mononuclear cells, inducing expression of the osteoclast markers RANK, <jats:italic>c<\/jats:italic>\u2010<jats:italic>src<\/jats:italic>, <jats:italic>c<\/jats:italic>\u2010<jats:italic>fos<\/jats:italic>, cathepsin\u2010K and TRAP. SJ\u2010N\u2010KP, which released both OPG and RANKL, did not show the same capability. OPG, neutralizing anti\u2010RANKL antibody and antisense oligonucleotides were evaluated for their ability to inhibit RANKL activity. The neutralizing antibody hampered osteoclastic differentiation by blocking both the juxtacrine and the paracrine activity of RANKL. Our findings confirm that neuroblastoma cells induce osteoclastogenesis <jats:italic>via<\/jats:italic> RANKL and suggest that the RANKL expression associated with lack of the decoy receptor OPG could be a peculiarity of some tumors that makes them able to induce metastatic osteolysis. Moreover, our results suggest that RANKL could be a relevant target in the adjuvant therapy of bone metastatic neuroblastoma as proper neutralization revokes completely osteoclastic differentiation. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20308","type":"journal-article","created":{"date-parts":[[2004,5,20]],"date-time":"2004-05-20T19:02:53Z","timestamp":1085079773000},"page":"829-838","source":"Crossref","is-referenced-by-count":45,"title":["<i>In vitro<\/i> blockade of receptor activator of nuclear factor\u2010\u03baB ligand prevents osteoclastogenesis induced by neuroblastoma 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