GDF15 Promotes Osteoclast Differentiation and High Serum GDF15 Levels Are Associated with Multiple Myeloma Bone Disease

摘要: Introduction Growth differentiation factor 15 (GDF15) is a multifunctional growth of the transforming beta (TGFbeta) family that plays complex role in several types cancers. In multiple myeloma, GDF15 was recently shown to enhance tumor-initiating and self-renewal potential cancer cells (Tanno et al, Blood 2014). Moreover, blood bone marrow plasma levels are elevated myeloma patients compared with healthy persons, high serum associated poor prognosis (Corre Cancer Research 2012). seems important for remodeling during hypoxia (Hino JBMR 2012), one study proposed increase osteoclast activation prostate metastasizing (Wakchoure Prostate 2009). Whether disease not well characterized. Aim Our aim investigate whether characterize effect on vitro. Methods measured samples obtained at diagnosis from 138 58 age sex-matched controls. The patient were collected Nordic Myeloma Study Group randomized phase 3 clinical trial which two different doses pamidronate bone. therefore particularly well-characterized this (Gimsing Lancet Oncol 2010). Peripheral mononuclear (PBMC) isolated buffy coats cultured medium (a-MEM human (20%), M-CSF (30ng/ml) RANKL (50ng/ml)) up 14 days or without GDF15. Purchased pre-osteoclasts (Lonza Inc.) purchased bullet kit (OC (33ng/ml) (66ng/ml)) 7 Cells positive tartrate resistant acidic phosphatase (TRAP) staining more than nuclei counted as osteoclasts. Results significantly higher (median 1.08 ng/ml, range 27.91) controls 0.46 1.66, Independent Kruskal-Wallis test p vitro, addition (0-100 ng/ml) precursors PBMC increased numbers multi-nucleated TRAP dose dependent manner (n=3, O ng/ml mean 25.7, SEM 5.9, 2 29.7, 4.3, 20 38.7, 4.9, 50 53.3, 11.6, 100 78.7 7.8). OPG inhibited pro-osteoclastogenic activity inferring mediated by RANKL. Hence, increases differentiation. Conclusion Serum advanced osteolytic no lesions. could play regulating patients. Disclosures No relevant conflicts interest declare.