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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4334-4337.
Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-09-3568.
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Submitted September 6, 2005
Accepted January 23, 2006
Imatinib as a potential anti-resorptive therapy for bone disease
Andrea L Dewar, Amanda N Farrugia, Mark R Condina, L. Bik To, Timothy P Hughes, Barrie Vernon-Roberts, and Andrew C Zannettino*
Myeloma & Mesenchymal Research Laboratory, Division of Haematology, Level 2 Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
Division of Haematology, Level 2 Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
* Corresponding author; email: andrew.zannettino{at}imvs.sa.gov.au.
Osteoclasts (OCs) are large multinucleated cells derived from progenitor cells of the monocyte-macrophage lineage. Signal transduction via the macrophage-colony stimulating factor (M-CSF) receptor, c-fms, is essential for OC formation. Since we have previously demonstrated inhibition of c-fms by imatinib, we examined the effect of imatinib on OC formation and activity. OC formation was not affected by concentrations of 1.0µM imatinib and lower, but was reduced by 75% at 3.0µM imatinib. In contrast, both the area of resorption and the number of resorption lacunae were reduced by 80% at 0.3µM imatinib, and no resorption was observed at concentrations above 3.0µM. A dose-dependent decrease in receptor activator of nuclear factor  B (RANK) expression was observed in OCs when cultured in the presence of imatinib, providing a mechanism for the decrease in OC function. In vivo analysis of the effect of imatinib on OC activity in adult mice following 8 weeks of imatinib treatment also demonstrated a decrease in OC activity. These results suggest that imatinib may have therapeutic value as an anti-osteolytic agent in diseases such as osteoporosis, metastatic bone disease and multiple myeloma.
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