Disease relevance of BMP2

• We thus sought to determine whether BMP2 stimulation alters PTEN protein levels in the breast cancer line, MCF-7 [1].
• MATERIALS AND METHODS: A producer cell (A549) was co-transfected with adenovirus vectors encoding BMP2 (AdBMP2) and BMP7 (AdBMP7) or, as controls, each vector alone, AdNull (with no transgene) or no virus [2].
• Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression [3].
• METHODS: Radical prostatectomy (RP) specimens from 74 patients with clinically localized PC (median follow-up 51 months, range 15-152), 44 benign prostatic hypertrophy (BPH) lesions, and 4 normal prostates (NPs) were assessed for BMP2, Smad8, and Smad4 expression using immunohistochemistry [3].
• However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences [4].

Psychiatry related information on BMP2

• Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7 [5].

High impact information on BMP2

• In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked [6].
• Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time [6].
• The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2 [7].
• Mesenchyme cells from Mf1lacZ embryos differentiate poorly into cartilage in micromass culture and do not respond to added BMP2 and TGFbeta1 [8].
• BMP2 treatment results in accumulation of MADR1 in the nucleus [9].

Chemical compound and disease context of BMP2

• Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells [10].
• Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells [11].
• BMP-2 decreased the phosphorylation of retinoblastoma (Rb) protein induced by treatment with DHT [12].
• Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4 [13].
• In an RTBM1 neuroblastoma cell line, hTTL was increased after treating the cells with bone morphogenetic protein 2 (BMP2) or all-trans retinoic acid (RA), which induced neuronal differentiation [14].

Biological context of BMP2

• However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis [15].
• We investigated the effect of BMP2, a member of these growth and differentiation factors, on mitogenic signal transduction pathways induced by platelet-derived growth factor (PDGF) in glomerular mesangial cells [16].
• Such changes in mRNA:protein interactions may influence the posttranscriptional mechanisms that control BMP2 gene expression [17].
• A common single nucleotide polymorphism (SNP) disrupts a putative posttranscriptional regulatory motif, an AU-rich element, within the BMP2 3'-UTR [17].
• Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFbeta family [18].

Anatomical context of BMP2

• The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2 [19].
• Incubation of mesangial cells with increasing concentrations of BMP2 inhibited PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at 250 ng/ml [16].
• Saos2 cells overexpressing mIkappaB (Saos2-mIkappaB) exhibit higher expression of osteoblast phenotypic genes such as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV) [20].
• Mouse myoblast cells (C2C12) transduced with this vector could produce and secrete biologically active BMP2 protein and induce osteogenic activity, which was confirmed by ELISA and alkaline phosphatase activity assay [21].
• Colonization of human gastric mucosa with H. pylori was associated with an increase in BMP2 expression due to influx of inflammatory cells that produce BMP2 [22].

Associations of BMP2 with chemical compounds

• In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4 [23].
• The presence or absence of osteogenic media (beta-glycerol phosphate and ascorbic acid) and/or with BMP2 did not stimulate osteoblastic gene expression in the Runx2-null cells [24].
• During the course of perinatal development of sympathetic neurons, BRINP1 is induced from earlier embryonic stage and further increased toward adult stage, while BRINP3 expressed from earlier stage is replaced by BRINP2 expression which increases postnatally in accordance with the action of BMP2 and RA [25].
• In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected [26].
• The addition of the highest dose of BMP2 enhanced oestradiol production (P < 0.05) without affecting the proliferation of the cells [27].

Physical interactions of BMP2

• BMP-2 effectively displaced [125]OP-1 binding to HBCs while TGF-beta 1 did not [28].
• As the first step to test this hypothesis, we demonstrate that MGP is a binding protein for 125I-BMP-2 [29].
• Many reviews have addressed events downstream of BMP-receptor binding but few deal with molecular cascades involved in BMP-2-induced osteogenesis [30].
• BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II [31].
• Furthermore, Scatchard analyses revealed that the numbers of FGF-2 binding sites were increased by approximately 40% after BMP-2 treatment [32].

Co-localisations of BMP2

• MGP colocalized intracellularly with BMP2 [33].

Regulatory relationships of BMP2

• These data indicate that BMP2 exposure can regulate PTEN protein levels by decreasing PTEN's association with the degradative pathway [1].
• BMP-2 stimulated PlGF expression in MG63 cells with an EC50 of about 50 ng/ml and mRNA levels peaked between 24 and 32 h after stimulation [34].
• BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture [35].
• Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications [36].
• Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing [37].

Other interactions of BMP2

• We found that exposure to BMP2 increased PTEN protein levels in a time- and dose-dependent manner [1].
• BMP-2 and BMP-4 induced expression of ALK1 in a dose-dependent fashion as determined by real-time PCR and immunoblotting [38].
• The present study shows that in addition to TGF-beta1 and -beta3, endoglin interacts with activin-A, bone morphogenetic protein (BMP)-7, and BMP-2 but requires coexpression of the respective ligand binding kinase receptor for this association [39].
• MGP has also been identified as an inhibitor of bone morphogenetic protein-2 (BMP-2) [38].
• RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2 [15].

Analytical, diagnostic and therapeutic context of BMP2

• This study is, to our knowledge, the first to establish the feasibility of AAV-based BMP2 gene therapy for endochondral ossification in immunocompetent animals [21].
• MGP/BMP2 colocalization was analyzed by confocal microscopy. gamma-Carboxylation activity was measured by incorporation of 14CO2 into FLEEL synthetic peptide [33].
• Polymerase chain reaction (PCR) and Western blotting showed that the BMP2/7 fusion gene construct led to the production of BMP2/7 heterodimers in A549 'producer' cells [40].
• HCAECs were treated with oxidized-low density lipoprotein (ox-LDL, 80 microg/mL) or tumor necrosis factor-alpha (TNFalpha, 10 ng/mL), and the expression of Cbfa1, BMP2, and MGP was quantified by real-time PCR [41].
• In this study, we investigated the expression of the BMP receptors (BMPRs) in sheep ovaries by immunohistochemistry and the effect of BMP2, a natural ligand for these receptors, on granulosa cells cultured in vitro [27].

References