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https://hdl.handle.net/2440/52537
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dc.contributor.author | Diamond, P. | - |
dc.contributor.author | Labrinidis, A. | - |
dc.contributor.author | Martin, S. | - |
dc.contributor.author | Farrugia, A. | - |
dc.contributor.author | Gronthos, S. | - |
dc.contributor.author | To, L. | - |
dc.contributor.author | Fujii, N. | - |
dc.contributor.author | O'Loughlin, P. | - |
dc.contributor.author | Evdokiou, A. | - |
dc.contributor.author | Zannettino, A. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Journal of Bone and Mineral Research, 2009; 24(7):1150-1161 | - |
dc.identifier.issn | 0884-0431 | - |
dc.identifier.issn | 1523-4681 | - |
dc.identifier.uri | http://hdl.handle.net/2440/52537 | - |
dc.description.abstract | The plasma cell (PC) malignancy, multiple myeloma (MM), is unique among hematological malignancies in its capacity to cause osteoclast (OC)-mediated skeletal destruction. We have previously shown that elevated plasma levels of PC-derived CXCL12 are associated with presence of X-ray detectable osteolytic lesions in MM patients. To further investigate this relationship, plasma levels of CXCL12 and βCrossLaps, a marker of bone loss, were measured. A strong correlation between levels of CXCL12 and OC-mediated bone resorption was identified. To confirm the OC-activating potential of MM PC-derived CXCL12 in vivo, we established a model of MM-mediated focal osteolysis, wherein MM PC lines, such as RPMI-8226, were injected into the tibias of nude mice. Implanting RPMI-8226 gave rise to osteolytic lesions proximal to the tumor, resulting in a 5% decrease in bone volume (BV) compared with vehicle control. Importantly, bone loss was significantly inhibited with systemic administration of the CXCL12/CXCR4 antagonist T140. Furthermore, implanting CXCL12-overexpressing RPMI-8226 cells resulted in a 13% decrease in BV and was associated with increased OC recruitment proximal to the tumor, increased serum matrix metalloproteinase activity, and increased levels of collagen I degradation products. These findings confirm our hypothesis that MM PC-derived CXCL12 stimulates the recruitment and activity of OC, thereby contributing to the formation of MM osteolytic lesions. | - |
dc.description.statementofresponsibility | Peter Diamond, Agatha Labrinidis, Sally K Martin, Amanda N Farrugia, Stan Gronthos, L Bik To, Nobutaka Fujii, Peter D O'Loughlin, Andreas Evdokiou and Andrew CW Zannettino | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Bone & Mineral Res | - |
dc.source.uri | http://dx.doi.org/10.1359/jbmr.090210 | - |
dc.subject | multiple myeloma | - |
dc.subject | stromal-derived factor-1α | - |
dc.subject | CXCL12 | - |
dc.subject | osteolysis | - |
dc.title | Targeted disruption of the CXCL12/CXCR4 axis inhibits osteolysis in a murine model of myeloma-associated bone loss | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1359/JBMR.090210 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Martin, S. [0000-0002-5700-3478] | - |
dc.identifier.orcid | Gronthos, S. [0000-0002-6225-3084] | - |
dc.identifier.orcid | Evdokiou, A. [0000-0001-8321-9806] | - |
dc.identifier.orcid | Zannettino, A. [0000-0002-6646-6167] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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