Circulating Dickkopf-1 Is Correlated with Bone Erosion and Inflammation in Rheumatoid Arthritis

Abstract

DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

Role of Dickkopf-1 and Musculoskeletal Ultrasound in Bone Loss in Rheumatoid Arthritis

“…Furthermore, analysis of musculoskeletal US scanning revealed that DKK-1 levels also showed a highly significant positive correlation with US joint erosions (r=0.718, P<0.001).This was in accordance with Orsolini et al, they reported that patients with erosions had serum levels of Dkk-1 slightly higher than those without erosions [19]. In the present study, there was a highly significant positive correlation between US score of bony erosions and Larsen score (r=0.683, p<0.001).…”

“…In the present study, mean serum Dkk-1 level, in patients was 3165.33 ± 258.441 pg/ml, while it was 1144.44 ± 1028.539 pg/ml in controls. There was a highly significant difference between them (P<0.001).This is in accordance with Orsolini et al, they showed that the mean serum level of Dkk-1 was significantly higher in RA patients than in healthy controls (p<0.001) [19]. In addition, authors previously assessed circulating Dkk-1 levels in patients with active RA compared with patients with OA and healthy individuals.…”

Inflammatory osteolysis: a conspiracy against bone

“…However, this conclusion is controversial, as others report that NF-κB positively affects osteogenesis (64). Given the central role of Wnt signaling in osteoblast differentiation, the failure of RA focal osteolysis to heal is perhaps more likely due to the osteogenic-suppressive properties of TNF-α mediated through its induction of dickkopf-1 (DKK-1), a potent inhibitor of Wnt activation (65)(66)(67). Interestingly, in contrast to TNF-α arrest, which suppresses osteoclastogenesis but does not increase bone formation, blockade of DKK-1 does both, thus repairing erosive lesions (66).…”

Osteoimmunology: from mice to humans

“…DKK-1 and sclerostin (SOST) bind to and inactivate signaling from LRP5/LRP6, 31 inhibiting bone formation. In RA an increase in DKK-1 and SOST has been shown, which blunts OB formation and activity and, together with the increase in bone resorption, is responsible for reduced bone mass 32 and for the formation of articular bone erosions. In fact, DKK-1 levels are associated with an increase in the number of articular erosions independently of age, baseline radiological features, C-reactive protein, or disease activity.…”