Interaction between Stromal Cell-Derived Factor 1 Alpha and Dickkopf-1 Involves in Occurence of Myeloma Bone Disease

Abstract

To explore the role of interaction between osteoclast stimulator stromal derived factor 1 alpha (SDF-1α) and osteoblast inhibitor dickkopf-1 (DKK-1) in the development of multiple myeloma (MM) bone disease. The serum samples of 51 patients with newly diagnosed MM, 30 age-matched healthy controls, and 35 non-Hodgkin lymphoma patients from June 2011 to May 2014 in Peking Union Medical College Hospital were collected. The serum SDF-1α and DKK-1 were detected by ELISA. Primary myeloma cells and human MM cell line RPMI 8226 were treated with SDF-1α, then DKK-1 mRNA expression was detected by real time PCR. Primary bone marrow stromal cells (BMSCs) were treated with Wnt-3a and/or DKK-1, and the transc-ription level of SDF-1α mRNA was assayed. Serum SDF-1α in MM patients was significantly higher than that in control group (3231.0±1269.5 pg/ml vs 2817.5±419.6 pg/ml)(P=0.036), so was serum DKK-1 (3057.4±1874.7 pg/ml vs 1867.7±1148.4 pg/ml)(P=0.01). There was a positive correlation between serum SDF-1α and DKK-1 in MM patients (r=0.301, P=0.032), but there was no correlation between control group (r=0.15, P=0.428) and non-Hodgkin lymphoma patients (r=0.227, P=0.095). After treated with SDF-1α (20 ng/ml) for 8 and 36 h, the DKK-1 mRNA transcription level in RPMI 8226 increased by 1.92 and 4.19-folds respectively(P=0.365, P=0.099). Moreover, the high transcription level of DKK-1 mRNA was observed in 5 out of 9 MM patients. The detection showed that after treatment with SDF-1α, the transcription level was up-regulated(P=0.043), the Wnt-3a (200 ng/ml) could decrease the expression of SDF-1α mRNA in primary BMSC to 29% of baseline(P=0.028), the adding DKK-1 could reverse the down-regulation effect. The serum SDF-1α and DKK-1 level in MM patients is high than normal leve, moreover shows the positive correlation between them. The SDF-1α and DKK-1 can interreact, therefore accerate the formation of MM bone disease.