{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:18:28Z","timestamp":1771503508645,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 \u03b2CrossLaps, 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.<\/jats:p>","DOI":"10.1359\/jbmr.090210","type":"journal-article","created":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T18:48:32Z","timestamp":1238525312000},"page":"1150-1161","source":"Crossref","is-referenced-by-count":59,"title":["Targeted Disruption of the CXCL12\/CXCR4 Axis Inhibits Osteolysis in a Murine Model of Myeloma-Associated Bone Loss"],"prefix":"10.1093","volume":"24","author":[{"given":"Peter","family":"Diamond","sequence":"first","affiliation":[{"name":"These authors contributed equally to this study"},{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agatha","family":"Labrinidis","sequence":"additional","affiliation":[{"name":"Discipline of Orthopaedics and Trauma, University of Adelaide, The Royal Adelaide Hospital and The Hanson Institute, Adelaide, Australia"},{"name":"These authors contributed equally to this study"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally K","family":"Martin","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda N","family":"Farrugia","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stan","family":"Gronthos","sequence":"additional","affiliation":[{"name":"Mesenchymal Stem Cell Group, Bone and Cancer Laboratories, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute and University of Adelaide, Adelaide, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L Bik","family":"To","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutaka","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto 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