Linked Life Data

19335218

Source:http://linkedlifedata.com/resource/pubmed/id/19335218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-6-24
pubmed:abstractText
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 betaCrossLaps, 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1523-4681
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1150-61
pubmed:meshHeading
pubmed-meshheading:19335218-Adult, pubmed-meshheading:19335218-Aged, pubmed-meshheading:19335218-Aged, 80 and over, pubmed-meshheading:19335218-Animals, pubmed-meshheading:19335218-Cell Line, Tumor, pubmed-meshheading:19335218-Chemokine CXCL12, pubmed-meshheading:19335218-Disease Models, Animal, pubmed-meshheading:19335218-Female, pubmed-meshheading:19335218-Humans, pubmed-meshheading:19335218-Male, pubmed-meshheading:19335218-Mice, pubmed-meshheading:19335218-Mice, Inbred BALB C, pubmed-meshheading:19335218-Mice, Nude, pubmed-meshheading:19335218-Middle Aged, pubmed-meshheading:19335218-Multiple Myeloma, pubmed-meshheading:19335218-Neoplasm Transplantation, pubmed-meshheading:19335218-Oligopeptides, pubmed-meshheading:19335218-Osteoclasts, pubmed-meshheading:19335218-Osteolysis, pubmed-meshheading:19335218-Receptors, CXCR4
pubmed:year
2009
pubmed:articleTitle
Targeted disruption of the CXCL12/CXCR4 axis inhibits osteolysis in a murine model of myeloma-associated bone loss.
pubmed:affiliation
Myeloma Research Program, Bone and Cancer Laboratories, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute and the Department of Medicine, University of Adelaide, Adelaide, Australia.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't