RANKL Is Critically Involved in the Physiopathology of Multiple Myeloma

摘要

The biological mechanisms involved in the pathogenesis of multiple myeloma (MM) bone disease are not completely understood. In the lasts years RANKL system lias been identified as critical in the regulation of bone resorption. Our data show that human MM cells did not directly express RANKL but up-regulated RANKL and inhibited its soluble antagonist osteoprotegerin (OPG) in bone marrow stromal cells through the cell to cell contact. Using a co-culture transwell system we also found that human myeloma cell lines (HMCL) increased the expression and secretion of RANKL in activated T lymphocytes and similarly purified MM cells stimulated RANKL production by autologous T lymphocytes. Moreover we found that the release of IFN-gamma by T lymphocytes was reduced by the presence of both HMCL and purified MM cells. The finding of RANKL mRNA overexpression observed in BM T lymphocytes of MM patients with severe osteolytic lesions in comparison to those without bone lesions support these observations.