High impact information on Gdf2

• The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2 [1].
• Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons [2].
• We measured gene expression patterns in septal cultures of embryonic day 14 mice and rats grown in the presence or absence of BMP9 by using species-specific microarrays and validated the RNA expression data of selected genes by immunoblot and immunocytochemistry analysis of their protein products [2].
• Furthermore, we demonstrated that BMP-9-regulated Id expression is Smad4-dependent [3].
• RNA interference-mediated knockdown of Id expression significantly diminished the BMP-9-induced osteogenic differentiation of mesenchymal progenitor cells [3].

Biological context of Gdf2

• Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration [4].
• However, whereas the basic signal transduction pathways for most known members of the TGF-beta superfamily have been well characterized in brain and other organs, nothing is known about the signal transduction pathway of BMP9 in the brain [5].
• These data show that BMP9 activates the canonical BMP signaling pathway and suggest that this could be one of the mechanisms responsible for the induction of the cholinergic phenotype by BMP9 in the basal forebrain [5].
• Upregulation of acetylcholine synthesis by bone morphogenetic protein 9 in a murine septal cell line [6].

Anatomical context of Gdf2

• Surprisingly, a constitutive overexpression of these Id genes also inhibited osteoblast differentiation initiated by BMP-9 [3].
• Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation [7].
• BMP-9 mRNA was exclusively detected in the liver of adult mice, whilst no expression was found in stromal cell lines propagated from day-16 fetal liver or neonatal or adult bone marrow [8].
• Bone morphogenetic protein 9 is a potent synergistic factor for murine hemopoietic progenitor cell generation and colony formation in serum-free cultures [8].
• 125I-BMP-9 bound specifically to a high percentage of blast cells in lineage-depleted post-fluorouracil bone marrow cells and to megakaryocytes in normal and post-fluorouracil bone marrow, indicating that BMP-9R are expressed on these cells [8].

Other interactions of Gdf2

• Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points [4].
• However, cross-competition experiments demonstrate that the BMP-9 receptors on HepG2 cells do not bind other BMPs or TGF-beta s, indicating that these are novel receptors with binding specificity for BMP-9 [7].
• In the presence of neutralizing antibodies (Ab) against TGF-beta1, BMP-9 concentrations of 3 ng or higher synergized with IL-3, SF+IL-3, SF+IL-11/12, or IL-3+SF+IL-11/12 to increase CFU-C generation [8].

Analytical, diagnostic and therapeutic context of Gdf2

• To determine whether the genes induced by BMP9 in culture were constituents of the BFCN transcriptome, we purified BFCN from embryonic day 18 mouse septum by using fluorescence-activated cell sorting of NGFR(+) cells and profiled mRNA expression of these and NGFR(-) cells [2].

References