Dickkopf-1 as a potential therapeutic target in Paget's disease of bone.
BACKGROUND
Wnt signalling plays a role in maintaining healthy bone mass. Dickkopf-1 (DKK-1) is a soluble inhibitor of Wnt signalling and its excessive expression contributes to bone loss in rheumatoid arthritis and multiple myeloma. New therapeutics have been developed for treatment of these conditions that target DKK-1 expression. DKK-1 is elevated in serum of patients with Paget's disease of the bone (PDB) and evidence is accumulating for a role of DKK-1 in PDB.


METHODS
The role of Wnt signalling and DKK-1 in bone health and disease and the aetiology of PDB in the light of recent advances in understanding of Wnt signalling.


RESULTS
PDB is a disorder of unknown aetiology characterised by localised increase in unregulated bone remodelling resulting in osteolytic and osteosclerotic lesions. Evidence is adduced for the involvement of Wnt signalling, DKK-1 and osteoblasts in PDB pathogenesis.


CONCLUSIONS
At present there is no cure for PDB and the current treatment of choice are bisphosphonates. These treat the resorptive phase of PDB but do not prevent its return. We present a new perspective on the aetiology of PDB and speculate on DKK-1 as a therapeutic target.
McCarthy
Helen S
HS
RJAH Orthopaedic Hospital, Charles Salt Centre, Oswestry, Shropshire, SY10 7AG, UK. Helen.mccarthy@rjah.nhs.uk
Marshall
Michael J
MJ
D000818:Animals; D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000209:etiology; D010010:Osteoclasts / Q000502:physiology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000502:physiology
C501126:DKK1 protein, human; D004164:Diphosphonates; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins