Dickkopf-1 (DKK-1) is an inhibitor of Wnt signaling pathway involved in the regulation of bone resorption, DKK-1 is associated with a variety of bone diseases such as rheumatoid arthritis, multiple myeloma, Paget’s disease and osteoporosis. Creative BioMart Biomarker offers high quality detection service for DKK-1, ensuring high detection accuracy, sensitivity and efficiency for each sample.
DKK-1 is a secreted protein with two cysteine rich regions and belongs to the DKK family. DKK family is mainly composed of DKK-1, DKK-2, DKK-3, DKK-4 and a DKK-3 related protein which is known as soggy. They can participate in physiological activities by inhibiting Wnt signaling pathway. Among them, DKK-1 is the better-studied member that was originally found in the Xenopus, it is widely expressed in osteoblasts, osteocytes, skin, prostate, placenta, etc. Wnt signaling pathway plays an important role in cell fate determination, cell proliferation, cell polarity, cell migration, embryonic development, stem cell maintenance and tissue repair in the case of injury. In general, the Wnt signal is initiated by the binding of Wnt proteins to Frizzled (Fzd) receptors which can bind to a coreceptor such as lipoprotein receptor related protein 5 and 6 (LRP5/6), to form a complex that activates the typical and atypical Wnt signaling pathways. Only when bind to Fzd and LRP5/6 simultaneously to form a receptor-ligand complex, can Wnt protein stimulate the Wnt signaling pathway. Wnt1 protein binds to β-propeller1 of LRP5/6, and Wnt3 binds to β-propeller3 of LRP5/6, while DKK-1 not only binds to β-propeller1 of LRP5/6, but also binds to β-propeller3. Since the interaction between Wnt protein and β-propeller is blocked, Wnt signaling pathway is suppressed. In addition, DKK-1 can also enhance its inhibitory function by using coreceptors. Wnt signaling pathway is an important regulator of bone development and bone balance, and it increases bone mass through a number of mechanisms, including stem cell turnover, stimulation of pre-osteoblastic replication, induction of osteoblastogenesis, and inhibition of apoptosis for osteoblasts and osteocytes. DKK-1 disrupts cascade reaction of Wnt signaling to inhibit osteoblast differentiation. Decreased expression of DKK-1 leads to an increase in Wnt activity and bone mass, while increased expression of DKK-1 may result in an increase in osteoblast-dependent osteoclastogenesis. Studies have shown that circulating DKK-1 levels are sufficient to reflect its expression in the bone microenvironment, therefore, DKK-1 is an important biomarker of bone resorption.
Figure 1. The prevailing model of the role of DKK-1 and the mesenchymal cell lineage in bone development and bone mass homeostasis (Pinzone, et al. 2008)
Creative BioMart Biomarker strictly controls each specific experimental step in the DKK-1 detection procedure to ensure accurately quantify the level of DKK-1 in each sample.
At Creative BioMart Biomarker, we offer DKK-1 detection service that includes several technical methods, you can communicate with our experts according to your research needs, and we will determine the final detection technological scheme based on the communication results. Please feel free to contact us, Creative BioMart Biomarker is here to offer you professional and thoughtful service.