Sandbox:Hannan

Molecular pathways and factors associated with osteoblastic activity

Association with multiple myeloma

Wingless and integration-1 (Wnt) signaling Activation of Wnt pathway → binding of Wnt ligands to Wnt co-receptors LRP5/6 and one trans-membrane receptor of the FDZ family → formation of complex that includes disheveled (DVL), Axin, FRAT1, and GSK-3β → translocation of β-catenin from cytoplasm to nucleus → activation of T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors → ↑ bone formation and ↓ bone resorption Binding of PTH to PTH1 receptor may result in activation of same receptor This pathway is also involved in cell-cycle promotion

Dickkopf 1 (Dkk-1), an extracellular inhibitor of this pathway expressed by osteoblasts and bone marrow stromal cells, is thought to play the crucial role in osteoblastic inhibition in multiple myeloma