Disease relevance of BMP4

• BMP4 is preferentially expressed in diffuse-type gastric cancer cells [1].

High impact information on BMP4

• Natural bovine osteogenin (BMP-3) and recombinant BMP-4 are equipotent in chemotaxis, limb bud chondrogenesis, cartilage maintenance, and in vivo bone induction [2].
• The influence of recombinant bone morphogenetic protein-4 and some related members, TGF-beta 1, activin A, and inhibin A, on articular chondrocyte metabolism in the presence and absence of extracellular matrix has been examined [3].
• Chemical cross-linking showed the presence of three components (apparent size 200, 90, and 70 kDa), demonstrating the presence of functional receptors for BMP-4 on primary articular chondrocytes [3].
• BMP-4 mRNA was expressed on Day 14 when the expression of the extracellular matrix proteins was increased [4].
• Binding experiments with 125I-BMP-4, revealed the presence of specific, high-affinity binding sites with an apparent dissociation constant of 110 pM and about 6000 receptors per cell [3].

Biological context of BMP4

• Comparative genomics on BMP4 orthologs [1].
• Here, vertebrate BMP4 orthologs were identified and characterized by using bioinformatics for comparative proteomics and comparative genomics analyses [1].
• Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development [5].
• Reverse transcription polymerase chain reaction studies with antral follicles showed the expression of BMPR-IA, BMPR-IB, ActR-IA, ActR-IIB, BMPR-II and BMP4 mRNA in all follicular compartments, while BMP2 mRNA was generally restricted to theca and cumulus tissue [5].
• Recombinant bone morphogenetic protein-4, transforming growth factor-beta 1, and activin A enhance the cartilage phenotype of articular chondrocytes in vitro [3].

Anatomical context of BMP4

• It is concluded that a BMP-signaling system, consisting of BMP2, BMP4, type II and I receptors, is present in bovine antral follicles and that this system plays a role in development and functioning of these follicles rather than in final oocyte maturation and cumulus expansion [5].
• The immunostaining of BMP2 and BMP4 was limited to theca interna and approximately 25% of oocytes of antral follicles [5].
• Exogenously added BMP2 or BMP4 to IVM medium did not affect oocyte nuclear maturation, cumulus cell expansion, nor blastocyst formation following IVF [5].
• In mice with inherited photoreceptor degeneration, there was a dramatic decrease in BMP4 mRNA in retina and RPE during and after the degeneration. mRNA for the type II BMP receptor was observed in freshly isolated and cultured RPE cells, isolated retina, and freshly isolated bovine aortic endothelial cells [6].
• The same cells express at least two potential ligands for these receptors (BMP-4 and -7), whereas bovine granulosa cells and oocytes express BMP-6 [7].

Associations of BMP4 with chemical compounds

• Thymidine incorporation in early-passage RPE cells showed a 14-fold stimulation above control with 5% serum that was decreased to 322%, 393%, and 313% in the presence of BMP-2 (10 ng/ml), BMP4 (10 ng/ml), and transforming growth factor (TGF)-,1 (2 ng/ml), respectively [6].
• Here we report that BMP-4, -6, and -7 potently suppress both basal (P < 0.0001; respective IC(50) values, 0.78, 0.30, and 1.50 ng/ml) and LH-induced (P < 0.0001; respective IC(50) values, 5.00, 0.55, and 4.55 ng/ml) androgen production by bovine theca cells while having only a moderate effect on progesterone production and cell number [7].

Other interactions of BMP4

• Gremlin and chordin were found to be effective antagonists of BMP-4 and -7, respectively, and the observation that both antagonists enhanced (P < 0.01) androgen production in the absence of exogenous BMP suggests an autocrine/paracrine role for theca-derived BMP-4 and -7 in modulating androgen production [7].
• We evaluated the effects of GDF-9 (150-600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation [8].
• Moreover, studies on granulosa cells showed that preincubation of ligand with excess FS abolished activin-A-induced phosphorylation of Smad-2 and BMP-4-induced phosphorylation of Smad-1 [9].

Analytical, diagnostic and therapeutic context of BMP4

• Immunocytochemistry revealed expression of BMP-4 and -7 in isolated theca cells whereas granulosa cells and oocytes selectively expressed BMP-6 [9].

References