Research Project
Grant-in-Aid for Challenging Exploratory Research
Multiple myeloma (MM) generates devastating bone destruction. We recently reported that TNFα converting enzyme (TACE) expression in monocytes cleaved their surface M-CSF receptor (M-CSFR), which drastically disrupts osteoclastogenesis(Blood, 2009). Because TACE activity is inhibited by TIMP3, we explored the role of BMSC-derived TIMP3 in monocytic differentiation into DC or OC in MM. This study clarified that TIMP3 over-produced in MM bone marrow microenvironment restores surface M-CSFR on monocytes to facilitate their downstream signaling, which causes extensive bone destruction and impaired DC differentiation in MM. TIMP3 may therefore become a novel target in the treatment of MM bone disease.
All 2012 2011 Other
All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (14 results)
Leukemia
Volume: 26 Issue: 9 Pages: 2124-2134
10.1038/leu.2012.78
Br J Haematol
Volume: 155 Issue: 3 Pages: 328-339
10.1111/j.1365-2141.2011.08844.x
Int J Hematol
Volume: 93 Issue: 6 Pages: 727-735
10.1007/s12185-011-0850-7
Volume: 94 Issue: 1 Pages: 63-70
10.1007/s12185-011-0885-9
Volume: 25 Issue: 7 Pages: 1182-1188
10.1038/leu.2011.60
Int J Hematol.
Volume: 94(1) Pages: 63-70
Volume: 93(6) Pages: 727-35