Alkaline Phosphatase Production Induced by BMP-4 and Neutralization by Mouse BMP-4 Antibody.|
Recombinant Mouse BMP-4 (Catalog # 5020-BP) induces alkaline phosphatase production in the ATDC5 mouse chondrogenic cell line in a dose-dependent manner (orange line). Alkaline Phosphatase Production elicited by Recombinant Mouse BMP-4 (20 ng/mL) is neutralized (green line) by increasing concentrations of Rat Anti-Mouse BMP-4 Monoclonal Antibody (Catalog # MAB50201). The ND50 is typically 1.5-9 µg/mL.
BMP-4 is a TGF-beta superfamily ligand that is widely expressed from early embryogenesis through adulthood. It plays an important role in mesenchyme formation, epidermal determination, suppression of neural induction, the development of multiple organs, and tissue repair (1-5). The mouse BMP-4 precursor contains a 273 amino acid (aa) propeptide and a 116 aa mature protein (6). The propeptide is cleaved intracellularly by furin or proprotein convertase 6, enabling the 15 kDa mature BMP-4 monomer to form an active disulfide linked homodimer or heterodimer with BMP-7 (7-9). Mature mouse and human BMP-4 share 98% aa sequence identity. Mouse BMP-4 shares 85% aa sequence identity with mouse BMP-2 and 35%-54% with other mouse BMPs. Compared to BMP-4 homodimers, BMP-4/BMP-7 heterodimers exhibit a greater potency in inducing osteogenic differentiation (9). In Xenopus, the heterodimers can also induce the formation of mesoderm, whereas BMP-4 homodimers only provide ventralizing signals for existing mesoderm (10). BMP-4 signals through tetrameric complexes composed of type I (primarily Activin RIA or BMPR-IA) and type II (primarily Activin RIIA or BMPR-II) receptors (11, 12). The bioavailability of BMP-4 is regulated by its interaction with multiple proteins and glycosaminoglycans (13-15).
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