Dickkopf-1 is a key regulator of myeloma bone disease: opportunities and challenges for therapeutic intervention.
Myeloma bone disease (MBD) is the most visible aspect of plasma cell myeloma (PCM), which is characterized by the displacement of hematopoiesis and the formation of osteolytic bone lesions. The secreted glycoprotein Dickkopf-1 (DKK1), an inhibitor of the Wnt signaling pathway, is broadly expressed in myeloma cells but highly restricted in normal tissues. DKK1 plays a critical role in several aspects of bone biology and actively participates in regulating MBD by inhibiting osteoblasts and by activating osteoclasts. Based on these findings, ongoing research has been targeting DKK1 to find novel therapeutic strategies for MBD, such as DKK1-neutralizing antibodies, proteasome inhibitors, and vaccines. All these strategies have produced encouraging clinical results and consequently, revealed the significance of DKK1 in MBD. This review discusses the recent advances in our understanding of the DKK1 pathway signaling and how DKK1 can be exploited in the therapeutic intervention of MBD.
Department of Clinical Hematology, Affiliated No. 2 Hospital, Xi'an Jiaotong University, 157 West Five Road, Xi'an 710004, People's Republic of China; Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Electronic address: zhoufuling@163.com.
Fuling
F
Zhou
Shan
S
Meng
Huanjin
H
Song
François X
FX
Claret
D000818:Animals; D001847:Bone Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
Antibody; DKK1; Myeloma bone disease; Proteasome inhibitor; Vaccine