C-reactive protein promotes bone destruction in human myeloma by stimulating myeloma cell production of osteolytic cytokines via the CD32A-p38MAPK-twist axis. Homo sapiens

Bone destruction is a hallmark of human myeloma and affects more than 80% of patients. Although it is well established that myeloma cells mediate bone destruction by activating osteoclasts, the mechanism how myeloma cells are regulated to do so is unknown. Here we show that C-reactive protein (CRP), a protein secreted in elevated amounts by hepatocytes in response to myeloma-derived cytokines, may be responsible for activating myeloma cells to promote osteoclastogenesis and inducing bone destruction in vivo. CRP binds to surface CD32A/FcRIIA, activates p38MAPK-twist pathways, and upregulates the secretion of osteolytic cytokines by myeloma cells. Clinical studies examining the relationship between the levels of serum CRP and the numbers of osteolytic bone lesions in newly diagnosed patients support this conclusion. Overall design: Three different human myeloma cell lines (ARP-1, MM.1S and U266) were treated with or without 5 ug/ml CRP for 24 hours. Then total RNA for myeloma cell lines or myeloma cell lines treated with CRP was extracted and used for comparison by gene expression profiling.