Disease relevance of BMP3

• Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate adenocarcinoma PAIII expressed predominantly BMP 3 mRNA [1].
• Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption [2].
• Osteogenin, and related bone morphogenetic proteins, induce endochondral bone differentiation through a cascade of events which include formation of cartilage, hypertrophy and calcification of the cartilage, vascular invasion, differentiation of osteoblasts, and formation of bone [3].
• The collagen-targeted BMP3 fusion protein (rhBMP3-C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo [4].
• OBJECTIVE: To explore reciprocal action between BMP-2 (bone morphogenetic protein-2) and BMP-3 for better understanding of the mechanism of BMP during bone fracture union [5].

High impact information on BMP3

• Two of the encoded proteins (BMP-2A and BMP-3) are new members of the TGF-beta supergene family, while the third, BMP-1, appears to be a novel regulatory molecule [6].
• Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta 1 transforming growth factor (TGF-beta 1) in human monocytes [7].
• Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade [7].
• Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression [7].
• The influence of osteogenin, purified from bovine bone, and of recombinant human bone morphogenetic protein-2B (BMP-2B) has been examined in bovine articular cartilage explants [8].

Biological context of BMP3

• In vitro data indicate that osteogenin stimulates the expression of the osteogenic and chondrogenic phenotypes [9].
• The sequences were similar to portions of the amino acid sequence deduced from the cDNA clone of bone morphogenetic protein-3 (BMP-3) [9].
• A comparison of genetic maps between bovine Chr 6 and human Chr 4 or mouse Chr 5 indicates possible candidate genes including FGFR3 and BMP3 genes, which are responsible for human chondrodysplasias and associated with bone morphogenesis, respectively [10].
• Furthermore, BMP3 is regulated in calvarial osteoblasts by recombinant human fibroblast growth factor 2 and by paracrine signaling from dura mater [11].
• These results extend previous observations of gene expression changes and reveal the in vivo regulation of BMP3 and multiple neuronal genes by PTH treatment [12].

Anatomical context of BMP3

• When a human bone marrow stromal cell (HBMSC) culture was treated simultaneously with 1,25(OH)2D3 (10(-8) M) and BMP3 (2.5 ng/ml), the total osteocalcin content in the cell layer and in the culture medium was higher than when the culture was treated with either factor alone (162%) [13].
• Opposing actions of BMP3 and TGF beta 1 in human bone marrow stromal cell growth and differentiation [14].
• A lot of reports have studied the presence of BMPs and their effects on bone marker expression in many different cell lines, however none describe the regulation of BMP3 by different factors and expression conditions [13].
• Osteogenin has been purified to homogeneity from bovine bone matrix and the sequences of several tryptic peptides have been determined [9].
• Stimulation of osteoblasts with recombinant human fibroblast growth factor 2 led to a rapid and sustained suppression of BMP3 expression (85 percent, p < 0.01) when compared with controls [11].

Associations of BMP3 with chemical compounds

• The bone inductive activity, termed osteogenin, can be dissociatively extracted, and it was isolated by heparin affinity, hydroxyapatite and molecular sieve chromatography [9].
• The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography [15].
• Simultaneous addition of 2.5 ng/ml osteogenin and 1,25 dihydroxy vitamin D3 (10(-8) M) enhanced the stimulation observed in osteocalcin synthesis [16].

Other interactions of BMP3

• This analysis reveals that the BMP2A and BMP3 genes map to conserved regions between mouse and human, while the BMP1 gene does not [17].
• After electrophoresis, RNA were blotted onto a nylon membrane and incubated with 32P-labeled BMP3 and GAPDH riboprobes [13].
• The carboxyl-terminal quarter of osteogenin has sequence identity to the corresponding regions of two related proteins BMP-2A and BMP-2B [9].
• Osteogenin fractions, with osteogenic activity in rats, were chromatographically adsorbed onto porous hydroxyapatites and implanted intramuscularly in baboons (Papio ursinus) [18].
• These results suggested that a number of candidate genes located in the excluded regions, such as the growth hormone (GH) gene, tumor necrosis factor-alpha (TNF-alpha) gene, and bone morphogenetic protein-3 (BMP3) gene, are unlikely to have a substantial effect on bone size variation in this Caucasian population [19].

Analytical, diagnostic and therapeutic context of BMP3

• To elucidate this synergistic activity, Northern blot analysis was done to study the effect of 1,25(OH)2D3 on BMP3 mRNA expression [13].
• Co-culture with dural cells decreased BMP3 mRNA by 50 percent compared with controls (p < 0.01) [11].
• The BMP-3 transcripts were detected with RT-PCR amplification followed by Southern blot hybridization, as well as by Northern and dot blot hybridization analyses [20].
• By in situ hybridization, the BMP-3 transcripts were found in lung bronchial epithelium, straight collecting kidney tubules, intestinal mucosa, perichondrium, periosteum, and osteoblasts of human embryos of 6-14 weeks' gestation [21].
• Molecular cloning of these polypeptides resulted in the identification of 4 previously undescribed genes (BMP-1, BMP-2A, BMP-2B, and BMP-3) each of which is capable of directing de novo cartilage formation in vivo [22].

References