Abstract:

Objective To investigate the role of MIP⁃1ɑ antagonist combined with bortezomib in the facili⁃ tation of osteoblasts in myeloma bone disease（MBD）by inhibiting Erk1/2/Bax. Methods A MBD mouse model was constructed by subcutaneous injection of myeloma cell lines. The mice were divided into four groups ：the control group，Bortezomib（Bor）group，MIP ⁃ 1ɑ antagonist（Bx471）group，Bor combined with Bx471（Bor + Bx471）group. Enzyme linked immunosorbent assay（ELISA）was used to detect the expression levels of MIP ⁃1ɑ， SOST，IL⁃6，BALP，RANKL，and OPG and Western blotting the expression levels of Erk，Bax，Caspase 3， Caspase 9，and X⁃ray to assess the degree of bone destruction. Results X⁃ray tests showed that the tumor⁃bearing mice in the control group had pathological fractures. As compared with the control group，the bone destructions in the other three groups were at a lower level. In contrast，the levels of MIP⁃1α，SOST，RANKL，and IL⁃6 in the control group were significantly higher than in Bor group and Bx471 group（P < 0.05），especially than in Bor+ Bx471 group（P < 0.001），while the expressions of OPG and BALP were significantly lower than in the Bor com⁃ bined with Bx471 group（P < 0.001）. The protein expressions of Erkl/2，Bax，Caspase 3，Caspase 9 in the control group were higher than in Bor group and Bx471 group（P < 0.05），especially than in Bor + Bx471 group（P < 0.001）. Conclusions MIP⁃1ɑ antagonists combined with bortezomib may inhibit the Erk1/2/Bax signaling pathway and then promote MBD osteoblasts. 

Key words:

MIP?1ɑ antagonist, bortezomib, myeloma bone disease, myeloma bone disease, Erk1/2/Bax