Table 1.
DKK1 features in MBD.
| Features | Details | References |
|---|---|---|
| Similarity | Belongs to the Dickkopf family. | 12 |
| Location | 10q21.1 | 16 |
| Protein | Size 266aa Signal peptide 1 to 24 aa, Low complexity region 45 to 57 aa, Dickkopf domain 84 to 140 aa |
11, 12 |
| Derivation | DKK1 is secreted by PCM and normal BM-MSCs. |
25 27 42 |
| Elevated levels | Bone marrow Plasma PCM cell lines Peripheral blood |
7 16, 17 22 39 42 43 44 45 |
| Protein binding | DKK1 interacts with LRP5/6; Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein Kremens that promotes internalization of LRP5/6. Transmembrane proteins Kremen1 and Kremen2 are high-affinity Dkk1 receptors that functionally cooperate with Dkk1 to block Wnt/beta-catenin signaling. |
2 18, 19 20, 21 |
| Signal transduction | Dkk-1 directly interrups Wnt-regulated differentiation of osteoblasts and indirectly enhances osteoclast function via a DKK1-mediated increase in RANKL-to-OPG ratios in PCM. |
30 39 40 |
| Function | Forced overexpression of Dkk1 in osteoblasts causes osteopenia, disruption of the hematopoietic stem cell niche, defects in HSC function. and also inhibits fracture repair. Knockdown of DKK1 expression in BM-MSCs decreased their ability to promote myeloma and the associated bone disease in mice. |
5–7 23 37 |