Secreted frizzled-related protein 3 (sFRP3) (sFRP3)

Secreted frizzled-related protein 3 (sFRP3), also known as FRZB, is a secreted glycoprotein that functions as a potent antagonist of the Wnt signaling pathway. It contains a cysteine-rich domain (CRD) that is highly homologous to the extracellular binding domain of Frizzled receptors, enabling it to sequester Wnt ligands and prevent their binding to cell-surface receptors (UniProt P41222). sFRP3 is primarily recognized for its essential role in skeletal development and the maintenance of articular cartilage, where it regulates chondrocyte differentiation and prevents cartilage degradation (PubMed: 15034578). Genetic variations in the FRZB gene, particularly the rs11177 polymorphism, have been significantly associated with an increased risk of osteoarthritis, positioning sFRP3 as a key therapeutic target for joint diseases (PubMed: 15034578, 17308176). In the context of oncology, sFRP3 often functions as a tumor suppressor; its downregulation or epigenetic silencing is observed in various cancers, leading to aberrant Wnt activation and tumor progression (PubMed: 21814189). While no FDA-approved drugs currently target sFRP3, research into recombinant sFRP3 proteins and gene therapy approaches aims to restore its inhibitory function in degenerative and malignant conditions.

Other names

FRZBFrizzled-related proteinFRZB1FREFritzhFrzbSFRP-3

Acts as a competitive antagonist of Wnt signaling by binding directly to Wnt ligands through its cysteine-rich domain (CRD), thereby preventing the ligands from interacting with Frizzled receptors and activating the canonical Wnt/beta-catenin pathway.