Related Experiment Video
Updated: Jun 17, 2026
Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Dickkopf-1 as a potential therapeutic target in Paget's disease of bone
Helen S McCarthy1, Michael J Marshall
1RJAH Orthopaedic Hospital, Charles Salt Centre, Oswestry, Shropshire, SY10 7AG, UK. Helen.mccarthy@rjah.nhs.uk
Importance Of The Field:
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.
Areas Covered In This Review:
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.
What The Reader Will Gain:
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.
Take Home Message:
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.
Insights
Dickkopf-1 (DKK-1), an inhibitor of Wnt signalling, is implicated in Paget's disease of the bone (PDB). Targeting DKK-1 may offer a new therapeutic strategy for PDB, a condition currently lacking a cure.
Area of Science:
- Bone biology and disease
- Endocrinology
- Rheumatology
Background:
- Wnt signalling is crucial for maintaining bone mass.
- Dickkopf-1 (DKK-1) inhibits Wnt signalling and its overexpression causes bone loss.
- Elevated DKK-1 levels are observed in Paget's disease of the bone (PDB).
Purpose of the Study:
- To review the role of Wnt signalling and DKK-1 in bone health and disease.
- To explore the aetiology of PDB in light of Wnt signalling.
- To discuss DKK-1 as a potential therapeutic target for PDB.
Main Methods:
- Literature review of Wnt signalling pathways.
- Analysis of DKK-1 expression in bone diseases.
- Examination of PDB pathogenesis.
Main Results:
- PDB is characterized by localized, unregulated bone remodeling.
- Evidence suggests Wnt signalling, DKK-1, and osteoblasts are involved in PDB.
- Osteolytic and osteosclerotic lesions are hallmarks of PDB.
Conclusions:
- Current PDB treatments, like bisphosphonates, manage symptoms but do not prevent recurrence.
- DKK-1 presents a novel therapeutic target for PDB.
- Further research into DKK-1's role could lead to effective PDB treatments.
Related Concept Videos
02:23Abnormal Proliferation
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include: