A Pilot Investigation Of The Mechanism In Multiple Myeloma Bone Disease

Multiple myeloma (MM) is characterized by cloning proliferation of terminally differentiated plasma cells. The bone destruction, which serves as a predominant clinical feature of MM patients, is closely related to prognosis. Osteoclast (OC) has been proved to be the major effector cell of myeloma bone disease (MBD) and activated by a series of cytokines. Osteoclastic bone resorption is significantly enhanced in the areas infiltrated by MM cells. Moreover, a vicious circle has also been certified between the bone destructive process and tumor progression. Consequently, to explore the mechanism of MBD will be helpful for effective targeted therapies and improving life quality of MM patients.Objective: To investigate the correlation between myeloma bone disease and theRANKL/OPG system as well as the osteoclast activating factor (OAF). And to explore the pathogenesis of myeloma bone disease, the biological characteristics of NSE, as well as the relationship between NSE and clinical stages of MBD.Methods; An ELISA method was used to examine the serum levels of NSE andIL-6 and their correlations with clinical stages and grades of myeloma bone disease in MM patients; Because of CD138 represents as a specific marker on the surface of myeloma cells, we obtained highly enriched myeloma cells through using anti-CD 138 antibody and immunomagnetic microbeads; Real time RT-PCR was applied to compare the mRNA expression of the RANKL,OPG,IL-6,MIP-1αand NSE in MM cell line (U266) and MM patients. Based on the data, we analyzed its levels in bone marrow microenvironment and the associations between myeloma bone disease and myeloma cells.Results: (1) An increasing tendency of serum levels of NSE and IL-6 were detected in MM patients samples and the supernatant of MM cell line (U266), as well as associated with the clinical stages and grades of myeloma bone disease; (2)The positive rate of CD138 MM cells before and after sorting were 25.13±10.50% and 84.50±5.15%, respectively; (3) RANKL and RANKL/OPG ratios were significantly up-regulated in MM patients compared with control group and OPG represented a decreasing trend, while RANKL was undetectable in MM cell line (U266). The mRNA transcriptional levels of IL-6 and MIP-1αwere higher in MM patients than those of the control group. Our data also suggest that NSE showed a rising tendency in some MM patients; (4) After sorting, the mRNA transcriptional levels of RANKL and OPG were notable lower than pre-sorting while MIP-1αwas rasied. There is no significant difference of NSE and IL-6 mRNA transcription levels before and after sorting.Conclusion: The pathogenesis of MM bone disease is an imbalance of bone metabolism, namely, the balance of RANKL/OPG system has been damaged; Overexpression of osteoclast activating factor (OAF) such as IL-6 and MIP-1αis closely related to the occurrence and the progress of MM bone disease; The up regulation of NSE may contributes to myeloma bone disease and stages, indicating that it is probably another critical cytokine which triggers bone damage.