OsteoporosisThe Emerging Role of Dickkopf-1 in Bone Biology: Is It the Main Switch Controlling Bone and Joint Remodeling?
Section snippets
Methods
We performed an extensive internet search (Medline) using the keywords Dickkopf-1 and the abbreviation DKK-1. The computerized search was supplemented by a manual one on the reference lists of the retrieved articles. A total of 248 articles were evaluated; selection was based on relevance to study subject.
Short Overview of the Wnt/β-Catenin Pathway
The Wnt proteins are a family of 19, so far, secreted growth factors that regulate key cellular functions (10). They are capable of binding to a coreceptor complex located at the cell surface, which consists of the low-density lipoprotein receptor-related proteins 5 or 6 (LRP5, LRP6), and a member of the frizzled (Fz) family of proteins. The activation of the pathway is tightly linked to cytoplasmic β-catenin levels and is shown in Figure 1.
The Wnt pathway is tightly regulated at multiple
Discussion
The discovery of DKK-1, a soluble inhibitor of the Wnt pathway, enhanced our understanding of bone physiology and its disturbances in pathologic conditions such as osteoporosis, joint remodeling in inflammatory arthritides, osteoarthritis, and malignant bone disease and opened new avenues toward more effective therapies. Evidence suggests that targeting DKK-1 may be a therapeutic approach in osteoporosis. DKK-1 inhibitors emerge as promising tools to enhance Wnt signaling and stimulate new bone
Conclusions
The role of DKK-1 in joint remodeling and bone mass regulation warrants further exploration, especially in humans, where data are scarce. It appears as an interesting target for the treatment of osteoporosis; moreover, inhibiting or enhancing the function of DKK-1 may be a way of altering the process of joint remodeling where needed. For example, mAb-based inhibition of DKK-1 may attenuate erosive disease and serve as an adjunct therapy in RA. On the other hand, enhancing/restoring the function
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Dickkopf-1 as a promising therapeutic target for autoimmune diseases
2022, Clinical ImmunologyCitation Excerpt :The Wnt signaling pathway takes an important part in embryogenesis, organogenesis and homeostasis [13,14]. By promoting osteoblastogenesis, the Wnt/β-catenin pathway signaling may cause new bone formation [16–21]. Also, the canonical Wnt/β-catenin pathway has been identified to play a crucial role in skeletal development and homeostasis in adults, and dysregulation of this signaling is associated with bone pathology [15].
Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice
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The authors have no conflicts of interest to disclose.