Disease relevance of Bmp2

• To investigate a possible biological function of the pro-form of bone morphogenetic protein (BMP)-2, a member of the TGF-beta family, mature BMP-2, proBMP-2, and the isolated pro-peptide were recombinantly produced in Escherichia coli cells, and a biophysical comparison was performed [1].
• After 0.5 and 3 days of exposure to hypoxia, upregulation of BMP-2 was observed in the intrapulmonary arteries [2].
• Inflammatory changes and fibrosis lead to delayed healing, triggered by bone morphogentic protein 2/4 (BMP2/4) and transforming growth factor (TGF)-beta(1) [3].
• In particular, growth/differentiation factor-5, bone morphogenetic protein-2, -4, -7 and -12 significantly increased the survival promoting effects of neurotrophin-3 and nerve growth factor on cultured dorsal root ganglion neurons [4].
• After twenty-four hours, each defect received a single, intralesional, percutaneous injection of adenovirus carrying bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it remained untreated [5].

Psychiatry related information on Bmp2

• Our results indicate that only bone morphogenetic protein-2 promoted the differentiation of GABAergic neurons, especially of the calbindin-positive subpopulation, the subset of projecting striatal neurons that degenerates in Huntington's disease [6].

High impact information on Bmp2

• The effects of BMP-2 on noggin transcripts were dependent on protein, but independent of DNA synthesis [7].
• By contrast, if the cells are exposed to saturating concentrations of both BMP2 and transforming growth factor beta1 (which promotes smooth muscle differentiation), the two factors appear codominant [8].
• Bone morphogenetic protein 2 (BMP-2), which induces osteoblast function, does not alter TGF-beta binding or biochemical activity in fibroblasts and has only small effects in less differentiated bone cells [9].
• Pretreatment with BMP-2 diminishes TGF-beta-induced DNA synthesis in osteoblast-enriched cultures but synergistically enhances its stimulatory effects on either collagen synthesis or alkaline phosphatase activity, depending on the present state of bone cell differentiation [9].
• Independent changes in type I and type II receptors for transforming growth factor beta induced by bone morphogenetic protein 2 parallel expression of the osteoblast phenotype [9].

Biological context of Bmp2

• The effects of bone morphogenetic protein-2 (BMP-2), -4, and -6 were tested on the differentiation of rat osteoprogenitor cells using a bone nodule-forming assay system, and the kinetics of their actions were investigated by double labeling for alkaline phosphatase (ALP) and bromodeoxyuridine (BrdU) uptake in log phase cultures [10].
• ProBMP-2 could be processed to an N-terminally truncated form of BMP-2, digit removed BMP-2 (drBMP-2), that possessed biological activity, i.e. it induced ectopic bone formation [1].
• Bone morphogenetic protein-2 induces proinflammatory endothelial phenotype [11].
• Western blotting showed that in CAECs and carotid arteries BMP-2 elicited phosphorylation of p42/44 MAP kinase, which was reduced by blocking MAP kinase kinase and PKC [11].
• Moreover, co-treatment experiments revealed that BMP-2, -4, and -6 each inhibit TGF-beta 1-modulated increases in SM22alpha reporter gene activity [12].

Anatomical context of Bmp2

• The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro [10].
• Administration of bone marrow stromal cells significantly (P<0.05) promoted the proliferating cell astrocytic differentiation, and increased bone morphogenetic protein 2/4, connexin-43 and synaptophysin expression in the ischemic boundary zone compared with the controls, respectively [13].
• Bone marrow stromal cells produce soluble factors including bone morphogenetic protein 2 and bone morphogenetic protein 4 (bone morphogenetic protein 2/4) in ischemic brain [13].
• BMP 2/4 expression was initially present in the regions surrounding mesenchymal precursor cells expressing ERK 1/2, but then developed most prominently within the cytoplasm of hypertrophic chondrocytes expressing ERK 1/2 late in distraction [14].
• On the contralateral side of the dorsum, platelet-enriched fibrin glue/bone marrow mesenchymal stem cells/BMP-2 composites were injected [15].

Associations of Bmp2 with chemical compounds

• In organ culture, BMP-2 substantially decreased relaxation of rat carotid arteries to acetylcholine and increased production of reactive oxygen species, events inhibited by pharmacologically blocking protein kinase C (PKC) or NAD(P)H oxidase [11].
• The Trm effects were synergistic with those of BMP-2 or -4, suggesting that this glucocorticoid may increase the cell responsiveness to these BMPs [16].
• Suppression of cell proliferation and subsequent maturation of GFAP-positive cells by 5-fluorodeoxyuridine or aminoadipic acid abolished the neuron survival-promoting effect of BMP 2 [17].
• METHODS: PDGF-AA, EGF, NGF, M-CSF, BMP-2, BMP-4, dexamethasone, and estrogen were tested for their ability to alter the spectrum of crystallins in explanted newborn rat lens epithelial cells or in vitro differentiating newborn rat lens fiber cells [18].
• The defects were filled with a hyaluronic acid polymer loaded with 0.01, 0.1, 1, or 10 microg of BMP-2 or -4 [19].

Enzymatic interactions of Bmp2

• Moreover, BMP-2 induced phosphorylated Trk immunoreactivity in cultured striatal neurones, suggesting that neurotrophins are involved in BMP-2 neurotrophic effects [20].

Regulatory relationships of Bmp2

• In conclusion, BMP-2 inhibits IGFBP-5 expression in Ob cells through pathways that are independent of its mitogenic activity and through mechanisms that may involve decreased transcription or altered RNA processing [21].
• Moreover, the effects of both TGFbeta(1) and BMP-2 on alpha1(I) collagen gene expression were markedly decreased in transfected ROS 17/2.8 cells expressing a dominant-negative MEK-1 [22].
• Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway [23].
• We propose that the induction of BMP-2 and -4 and their receptor by GH compliments the role of GH-induced insulin-like growth factor 1 (IGF-1) in promoting bone and tooth root formation [24].
• In conclusion, this study demonstrates that BMP-2 and TGFbeta1 suppress collagenase-3 promoter activity in osteoblasts and establishes a link between BMP-2 action and collagenase-3 expression via Runx2, a major regulator of osteoblast formation and function [25].

Other interactions of Bmp2

• Continuous or 24-h exposure to BMP-2 or -4 increased the number of postmitotic ALP-positive cells in log phase cultures, whereas BMP-6 increased the number of postmitotic ALP-negative cells [10].
• BMP-2 showed reduced potency compared to either BMP-4 or -6 [10].
• Adjacent sections examined for BMP 2/4 expression established a close temporal and spatial correlation with ERK 1/2 [14].
• The expression of BMP2/4 subsequently increased the phosphorylation of downstream effector Smad1 and the expression of notch signal pathway-induced protein Hes1 in cultured SVZ neurospheres [26].
• The temporospatial expression of BMPs and receptors at the injured growth plate suggests potential involvement of BMP-3 and -4 in regulating the inflammatory response or as its mediators in modulating downstream events, and BMP-2, -3, -4, and -7 in the fibrogenic and osteogenic responses, and BMP-7 in bone remodeling at the injured growth plate [27].

Analytical, diagnostic and therapeutic context of Bmp2

• CONCLUSIONS: These data provide evidence that ERK 1/2 expression is present within mesenchymal precursor cells during distraction osteogenesis and that ERK expression correlates closely with BMP 2/4 expression [14].
• Quantitative real-time RT-PCR showed that the expression of BMP2/4 mRNAs decreased within ischemic astrocytes, In contrast, BMP2/4 mRNA was significantly increased after cocultured with BMSCs [26].
• Tissues were analyzed using immunohistochemistry for BMP ligand (BMP2, BMP4, BMP7) and receptor (BMPRIA, BMPRIB, BMPRII) expression [28].
• By 4 days after osteotomy, BMP-2 and BMP-4 mRNAs were detected in chondrogenic precursor cells in the subperiosteal immature callus [29].
• Bone lengthening with osteotomy and gradual distraction was achieved in 57 rats, and the effect of mechanical tension-stress on gene expression of bone morphogenetic proteins (BMPs) was investigated by in situ hybridization and Northern blot analysis using probes of BMP-2, BMP-4, BMP-6, BMP-7, and growth/differentiation factor (GDF)-5 [29].

References