Sclerostin and DKK-1 emerging biomarkers for bone disease

Bone markers are currently used to monitor skeletal diseases and treatments. The proteins Sclerostin and Dickkopf-1 (DKK-1) reflect distinct biological processes and have gained attention as potential biomarkers for bone-related conditions. They may provide valuable information for diagnosis, prognosis, and monitoring of bone diseases and treatments.

Sclerostin and DKK-1 emerging biomarkers for bone disease

Sclerostin and Dickkkopf-1 are two important osteocyte proteins that are involved in the regulation of bone metabolism, particularly through their interactions with the Wnt signaling pathway.

SCLEROSTIN (SOST) is a glycoprotein that is primarily secreted by osteocytes, the most abundant cells in bone tissue. It inhibits Wnt signaling, which is a critical pathway regulating bone formation and remodeling. Sclerostin acts as a negative regulator of bone formation by binding to the LRP5/6 co-receptors (low-density lipoprotein receptor protein), which activate Wnt signaling. By binding to LRP5/6, sclerostin inhibits the interaction between Wnt ligands and the Frizzled receptor, thereby inhibiting Wnt signaling and suppressing bone formation. Inhibition of Sclerostin has led to the development of a novel anabolic therapy for osteoporosis.

DICKKOPF-1 (DKK-1) is a protein that also inhibits the Wnt signaling pathway. DKK-1 binds to the LRP5/6 co-receptors thereby preventing Wnt ligand interaction thus inhibiting bone formation and promoting bone resorption.

The Wnt-signaling pathway is one of the most important pathways controlling bone metabolism. Sclerostin and Dickkopf-1 act as Wnt inhibitors and play a crucial role in controlling bone formation and resorption.

Sclerostin and DKK-1 can easily be measured in blood samples with an ELISA assay

BIOMEDICA offers two kits to measure Sclerostin

Bioactive Sclerostin ELISA cat. no. BI-20472

• serum, plasma, cell-culture
• characterized antibodies
• day test
• 20µl sample volume
• sample values provided
• full validation package

 

The epitope of the monoclonal capture antibody is in loop 2 of the Sclerostin molecule, which is the binding site for the LRP5/6 complex.

All Sclerostin molecules including potential fragments containing this receptor binding region can be detected.

Bioactive Sclerostin ELISA – antibody binding sites

 

Sclerostin ELISA cat. no. BI-20492

• most referenced more than 280 citations
• 20µl sample volume
• for serum, plasma
• full validation package

 

DKK-1 ELISA cat. no. BI-20413

• widely cited
• day test
• no sample dilution
• full validation package

 

All assays are developed and manufactured by BIOMEDICA

Related Publications

New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1). Dincel AS, Jørgensen NR; IOF-IFCC Joint Committee on Bone Metabolism (C-BM). Calcif Tissue Int. 2023 Feb;112(2):243-257. doi: 10.1007/s00223-022-01020-9. Epub 2022 Sep 27. PMID: 36165920.

Abstract

A healthy skeleton depends on a continuous renewal and maintenance of the bone tissue. The process of bone remodeling is highly controlled and consists of a fine-tuned balance between bone formation and bone resorption. Biochemical markers of bone turnover are already in use for monitoring diseases and treatment involving the skeletal system, but novel biomarkers reflecting specific biological processes in bone and interacting tissues may prove useful for diagnostic, prognostic, and monitoring purposes. The Wnt-signaling pathway is one of the most important pathways controlling bone metabolism and consequently the action of inhibitors of the pathway such as sclerostin and Dickkopf-related protein 1 (DKK1) have crucial roles in controlling bone formation and resorption. Thus, they might be potential markers for clinical use as they reflect a number of physiological and pathophysiological events in bone and in the cross-talk with other tissues in the human body. This review focuses on the clinical utility of measurements of circulating sclerostin and DKK1 levels based on preanalytical and analytical considerations and on evidence obtained from published clinical studies. While accumulating evidence points to clear associations with a number of disease states for the two markers, and thus, the potential for especially sclerostin as a biochemical marker that may be used clinically, the lack of standardization or harmonization of the assays still hampers the clinical utility of the markers.

 

Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration. Nelson AL, Fontana G, Miclau E, Rongstad M, Murphy W, Huard J, Ehrhart N, Bahney C. J Tissue Eng Regen Med. 2022 Nov;16(11):961-976. doi: 10.1002/term.3349. Epub 2022 Sep 16. PMID: 36112528; PMCID: PMC9826348.