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The objective of this study is to determine the role of BSP overexpression in osteolytic metastasis using two homozygous transgenic mouse lines in which BSP expression is elevated either in all the tissues (CMV\u2010BSP mice) or only in the osteoclasts (CtpsK\u2010BSP mice). The results showed that skeletal as well as systemic metastases of 4T1 murine breast cancer cells were dramatically increased in CMV\u2010BSP mice. In CtpsK\u2010BSP mice, it was found that targeted BSP overexpression in osteoclasts promoted in vitro osteoclastogenesis and activated osteoclastic differentiation markers such as Cathepsin K, TRAP and NFAT2. MicroCT scan demonstrated that CtpsK\/BSP mice had reduced trabecular bone volume and bone mineral density (BMD). The real\u2010time IVIS Imaging System showed that targeted BSP overexpression in osteoclasts promoted bone metastasis of breast cancer cells. The osteolytic lesion area was significantly larger in CtpsK\/BSP mice than in the controls as demonstrated by both radiographic and histomorphometric analyses. TRAP staining demonstrated a twofold increase in the number of osteoclasts in the bone lesion area from CtpsK\/BSP mice compared with that from wild type mice. We conclude that host tissue\u2010derived BSP also plays important roles in breast cancer metastasis through inducing tumor cell seeding into the remote host tissues. Furthermore, osteoclast\u2010derived BSP promotes osteoclast differentiation in an autocrine manner and consequently promotes osteolytic bone metastasis of breast cancer. J. Cell. Physiol. 218: 135\u2013145, 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21576","type":"journal-article","created":{"date-parts":[[2008,8,28]],"date-time":"2008-08-28T13:19:17Z","timestamp":1219929557000},"page":"135-145","source":"Crossref","is-referenced-by-count":34,"title":["Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer 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