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Chordin-like protein 2 (CHRDL2), also known as Breast tumor novel factor 1 (BNF1), is a secreted glycoprotein that functions as a key modulator of the Bone Morphogenetic Protein (BMP) signaling pathway (UniProt Q96BQ3). It contains three von Willebrand factor type C (VWC) domains, which allow it to bind directly to BMP ligands such as BMP-2, BMP-4, and BMP-7, effectively sequestering them and preventing their interaction with cell surface receptors (NCBI Gene ID: 25884). This antagonistic activity plays a significant role in regulating chondrogenesis, bone formation, and the maintenance of the extracellular matrix in connective tissues (PubMed: 11597505). In disease states, CHRDL2 is notably upregulated in osteoarthritic cartilage, where it is thought to impair the anabolic effects of BMPs on chondrocyte repair (PubMed: 24557778). Furthermore, its expression is linked to the progression of various malignancies, including breast and colorectal cancers, where it may influence tumor cell proliferation and metastasis (PubMed: 32454321). As a secreted protein involved in both degenerative and neoplastic processes, CHRDL2 represents a potential therapeutic target for biologics designed to restore BMP signaling or inhibit tumor growth.
Antagonism of Bone Morphogenetic Protein (BMP) signaling by direct binding to BMP ligands (e.g., BMP-2, BMP-4, and BMP-7), thereby preventing their interaction with cell surface receptors (PubMed: 11597505).
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