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- Title
C-reactive protein promotes bone destruction in human myeloma through the CD32-p38 MAPK-Twist axis.
- Authors
Jing Yang; Zhiqiang Liu; Huan Liu; Jin He; Jianling Yang; Pei Lin; Qiang Wang; Juan Du; Wencai Ma; Zheng Yin; Eric Davis; Robert Z. Orlowski; Jian Hou; Qing Yi
- Abstract
Bone destruction is a hallmark of myeloma and affects 80% of patients. Myeloma cells promote bone destruction by activating osteoclasts. In investigating the underlying mechanism, we found that C-reactive protein (CRP), a protein secreted in increased amounts by hepatocytes in response tomyeloma-derived cytokines, activated myeloma cells to promote osteoclastogenesis and bone destruction in vivo. In mice bearing human bone grafts and injected with multiple myeloma cells, CRP bound to surface CD32 (also known as FcgRII) on myeloma cells, which activated a pathway mediated by the kinase p38 MAPK and the transcription factor Twist that enhanced the cells' secretion of osteolytic cytokines. Furthermore, analysis of clinical samples fromnewly diagnosedmyeloma patients revealed a positive correlation between the amount of serum CRP and the number of osteolytic bone lesions. These findings establish a mechanism by which myeloma cells are activated to promote bone destruction and suggest that CRP may be targeted to prevent or treat myeloma-associated bone disease in patients.
- Subjects
C-reactive protein; MYELOMA proteins; CD antigens; LIVER cells; OSTEOCLASTOGENESIS; TREATMENT of bone diseases
- Publication
Science Signaling, 2017, Vol 10, Issue 509, p1
- ISSN
1945-0877
- Publication type
Article