Disease relevance of BMP6

• Furthermore, this coinactivation of BMP3b and BMP6 is significantly associated with mutation of k-ras codon 12 in lung cancer (P=0.003); those with a k-ras mutation were six times more likely to have concurrent methylation of these BMP loci [1].
• Cultured BMDMSC were transduced with E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days [2].
• Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism [3].
• We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites [3].
• Osteogenic protein-1 stimulates mRNA levels of BMP-6 and decreases mRNA levels of BMP-2 and -4 in human osteosarcoma cells [4].
• These data demonstrate that BMP-6 promotes migration and invasion of prostate cancer cells, potentially through activation of Id-1 and MMP activation [5].

High impact information on BMP6

• Bone morphogenetic protein-6 production in human osteoblastic cell lines. Selective regulation by estrogen [6].
• 17beta-estradiol increased BMP-6 protein production sixfold by Western analysis [6].
• These data suggest that some of the skeletal effects of estrogen on bone and cartilage may be mediated by increased production of BMP-6 by osteoblasts [6].
• Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo [7].
• Recombinant noggin inhibited the function of BMP-6, suggesting a negative feedback regulation of BMP activity and indicating a strategy for the development of a novel therapeutic target in the treatment of painful osteosclerotic bone metastases of prostate cancer [8].

Chemical compound and disease context of BMP6

• The effects of 17beta-estradiol (E2) and ICI 182,780 (ICI) on activity of a BMP-6 promoter were compared in osteoblast-like and breast cancer cells transiently transfected with ERalpha [9].
• In further studies where we compared the intracellular distribution of ERalpha associated with these responses, E2-dependent stimulation of the BMP-6 reporter in MCF-7 cells was associated with intranuclear localization of ERalpha, whereas extranuclear localization was seen in rat osteosarcoma cells (ROS) cells treated with ICI [9].
• Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively) [10].
• BMP-6 and retinoic acid synergistically differentiate the IMR-32 human neuroblastoma cells [11].

Biological context of BMP6

• Possible effects of BMP6 on TGF-beta-induced gene expression were examined in cultured renal fibroblasts (TK173 cells) [12].
• Bioassays revealed that FSH enhances BMP-induced SMAD1/5/8 phosphorylation and cellular DNA synthesis induced by BMP6 and BMP7 [13].
• Based upon a high degree of amino acid sequence homology, BMP5, BMP6, and BMP7 constitute a subfamily within the BMPs [14].
• This analysis reveals that BMP6 maps to a conserved region between the mouse and human genomes [14].
• Although both types of viruses induced an immune response in immunocompetent animals, this response played different roles in the process of bone formation induced by the BMP6 vectors [15].

Anatomical context of BMP6

• Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did [16].
• We investigated whether BMP6 is epigenetically inactivated in cell lines and whether BMP3b and BMP6 are epigenetically inactivated in non-small-cell lung cancer (NSCLC) [1].
• In the present study, we used fetal rat secondary calvarial cultures to study the role of BMP-6 during early osteoblast differentiation [17].
• DVR/BMP 6 protein was distributed in the early dental epithelium and, later, in pre-odontoblasts and odontoblasts, where it remained during dentin formation [18].
• Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6 [19].

Associations of BMP6 with chemical compounds

• Inhibition of endogenous BMP-6 action by neutralizing antibodies impaired aldosterone production induced by Ang II but not that induced by K [20].
• Involvement of bone morphogenetic protein-6 in differential regulation of aldosterone production by angiotensin II and potassium in human adrenocortical cells [20].
• Treatment with the GC triamcinolone (10(-9) M) resulted in a 5- to 8-fold increase in BMP-6 steady-state messenger RNA levels, peaking at 12 h [17].
• Here, we investigated functional roles of BMP-6, focusing on the differential regulation of aldosterone synthesis induced by angiotensin (Ang) II and potassium (K) [20].
• In contrast, transcripts for Growth/ Differentiation factor-S (GDF-5) were induced during a cellular condensation, and those for BMP-6 were induced during the formation of cartilage nodules, and declined as the differentiated ATDC5 cells became hypertrophic, and BMP-7 transcripts were only detected after cells became calcified [21].

Physical interactions of BMP6

• As a member of the TGF-beta super-family, BMP-6 binds to both BMP type I and type II receptors and is involved in the developmental processes of renal and hepatic systems as well as of human foetal intestine [22].

Regulatory relationships of BMP6

• In human adrenocortical H295R cells, BMP-6 augmented Ang II-induced CYP11B2 transcription and mRNA and aldosterone production but had no effect on K-induced aldosterone production [20].
• Replacement of BMP6 to SCG explant preparations significantly blunted the injury-induced elevated PACAP expression, with a concomitant decrease in sympathetic PACAP-immunoreactive neuron numbers [23].
• Recent work has shown that BMP3b is epigenetically inactivated in cancer and suggests that BMP6 can be epigenetically inactivated [1].
• These findings suggest various BMPs and activin A as components of the conjunctival cytokine meshwork regulating tissue homeostasis and wound healing and provide evidence that alterations in the expression of BMP-6 and activin A, in particular, are associated with conjunctival scarring [24].
• Furthermore, in CD10(+) B progenitors as well as in Nalm-6 cells, BMP-6 rapidly induced phosphorylation of Smad1/5/8, followed by an upregulation of Id1 and Id3 mRNA levels [25].

Other interactions of BMP6

• Importantly, myeloma cells not responsive to BMP-2 and -4 may still be sensitive to BMP-6 or -7 [26].
• In this study, we examined the effects on human myeloma cells of BMP-6 and -7, members of a different BMP subgroup, which mainly utilize Alk-2 as their receptor [26].
• Alk-2-expressing cell lines responded with growth inhibition and apoptosis to BMP-6 and -7, whereas cell lines lacking both Alk-3 and -6 were resistant to BMP-4 [26].
• Here, we demonstrate that the BMP3b and BMP6 genes are common targets of epigenetic inactivation in NSCLC, and that they are significantly more likely to be concurrently inactivated (P=0.009) [1].
• The mRNA and protein expression of both BMP-6 and activin A was found to be significantly increased in scar tissue compared with normal conjunctiva and could be immunolocalized to epithelial cells, vascular endothelia, stromal fibroblasts, and macrophage-like cells [24].

Analytical, diagnostic and therapeutic context of BMP6

• Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors [27].
• By immunohistochemistry, BMP-2 and BMP-6 were detected in the hyperplastic lining and the sublining layer of synovium from RA and SpA patients, both in CD90+ cells (FLS) and in some CD68+ cells (macrophages) [28].
• In situ hybridization was utilized to confirm the presence of BMP-2, BMP-4, and BMP-6 mRNA in 2- to 3-week-old mouse tibial marrow megakaryocytes [29].
• Molecular cloning and analysis of the 5'-flanking region of the human bone morphogenetic protein-6 (BMP-6) [30].
• Since BMP are currently being used in clinical trials for bone repair and fracture healing, the present results suggest a possible role for BMP-6 in mobilising CD34 positive cells for transplantation [22].

References