|BMP‑3 in Human Prostate Cancer Tissue. BMP‑3 was detected in immersion fixed paraffin-embedded sections of human prostate cancer using 15 µg/mL Goat Anti-Human BMP‑3 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF113) overnight at 4 °C. Tissue was stained with the Anti-Goat HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS008) and counterstained with hematoxylin (blue). View our protocol for Chromogenic IHC Staining of Paraffin-embedded Tissue Sections.|
BMP-3, also known as osteogenin, the most abundant BMP in adult bone, is one of at least 15 structurally and functionally related BMPs, which are members of the TGF- beta superfamily (1‑3). BMPs were originally identified as protein regulators of cartilage and bone formation. They have since been shown to be involved in embryogenesis and morphogenesis of various tissues and organs. BMPs also regulate the growth, differentiation, chemotaxis, and apoptosis of various cell types. Similar to most other TGF-beta family proteins, BMPs are highly conserved across animal species. At the amino acid sequence level, mature human and rat BMP-3 are 98% identical. BMP-3 is synthesized as a large precursor protein that is cleaved at the dibasic cleavage site (RXXR) to release the carboxy-terminal domain. Biologically active BMP-3 is a disulfide-linked homodimer of the carboxy-terminal 110 amino acid residues that contains the characteristic seven conserved cysteine residues involved in the formation of the cysteine knot and the single interchain disulfide bond (4). The role of BMP-3 in bone is contradictory since, unlike osteogenin purified from bone, recombinant BMP-3 has not shown osteogenic function (5). Several studies indicate that BMP-3 is an inhibitor of osteogenic BMPs. BMP-3 dorsalizes Xenopus embryos, the opposite effect of BMP-2 or 4, which cause ventralization. BMP-3 inhibits alkaline phosphatase production and induction of osteoblastic target genes in undifferentiated mesenchymal and osteogenic cell lines that have been treated with BMP-2. BMP-3 also induces the expression of TGF‑ beta /activin responsive genes, but not BMP-responsive genes. Since the inhibitory effect is not due to direct competition with osteogenic BMPs, it has been suggested that BMP-3 activates signaling through an activin pathway, resulting in antagonism of osteogenesis induced by other BMPs.