C-reactive protein promotes bone destruction in human myeloma through the CD32–p38 MAPK–Twist axis

Year: 2017

Type: article

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 to myeloma-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 FcγRII) 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 from newly diagnosed myeloma 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.

Source: Science Signaling

DOI: 10.1126/scisignal.aan6282

Authors: Jing Yang, Jing Yang, Zhiqiang Liu, Huan Liu, Jin He, Jianling Yang, Jianling Yang, Pei Lin, Qiang Wang, Juan Du, Wencai Ma, Zheng Yin, Eric Davis, Robert Z. Orlowski, Jian Hou, Qing Yi

Institutions: The University of Texas MD Anderson Cancer Center, Guangzhou Medical University Cancer Hospital, Guangzhou Medical University, Tianjin Medical University, Cleveland Clinic, Second Military Medical University, Shanghai Changzheng Hospital, Houston Methodist

Language: English

Topic: Multiple Myeloma Research and Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Cancer Society, Multiple Myeloma Research Foundation, American Society of Hematology, Leukemia and Lymphoma Society, Leukemia Research Foundation, National Natural Science Foundation of China, National Institutes of Health, University of Texas MD Anderson Cancer Center, National Cancer Institute

OpenAlex ID: W2772258348