Disease relevance of Bmp6

• Bone morphogenetic proteins (BMP6 and BMP7) enhance the protective effect of neurotrophins on cultured septal cholinergic neurons during hypoglycemia [1].
• Immunolocalization of vgr (BMP-6, DVR-6), a TGF-beta related cytokine, to Schwann cells of the rat peripheral nervous system: expression patterns are not modulated by autoimmune disease [2].
• Taken collectively, these results suggest that a mild and reversible ischemia stimulates the release of BMP-6 from neurons into the interstitial space [3].
• Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats [4].

High impact information on Bmp6

• As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA accumulation [5].
• This BMP-6 activity resembles BMP-15 but differs from GDF-9 activities [5].
• BMP-6 also decreased FSH- and forskolin-stimulated cAMP production, suggesting that the underlying mechanism by which BMP-6 inhibits FSH action most likely involves the down-regulation of adenylate cyclase activity [5].
• The signals of BMP-6 and GDF-5 mRNA declined by this stage, while those of BMP-2 and BMP-4 were maintained at high level for as long as distraction was continued [6].
• BMP-2, BMP-4, BMP-6, nor GDF-5 was expressed at this stage [6].

Biological context of Bmp6

• BMP-5 mRNA expression increased during the mineralization phase and BMP-6 mRNA expression increased throughout all phases of cell differentiation [7].
• Depolarization differentially regulates the effects of bone morphogenetic protein (BMP)-2, BMP-6, and activin A on sympathetic neuronal phenotype [8].
• Pharmacological suppression of cell proliferation or glial development abolished the induction of serotonergic markers by BMP-6 and -7, suggesting that BMPs act indirectly by stimulating synthesis or release of glial-derived serotonergic differentiation factors [9].
• NGF-increased phosphorylation of p44(Erk1) and p42(Erk2) between 2 and 24h was unaffected by addition of BMP6 [10].
• BMP-7 promotes cell survival, with a maximal effect at 10 ng/ml, whereas tenfold more BMP-6 is needed: Both were active over the course of 8 days in culture [11].

Anatomical context of Bmp6

• The results demonstrate that BMP-6, like other BMPs, can stimulate osteoblast differentiation independent of any chondrogenic effects and suggest that an early osteoprogenitor cell is an important target cell for the action of BMPs during bone induction [12].
• Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1 [13].
• Specifically, we show that BMP 2 and BMP 6 are expressed in the developing midbrain floor of the rat [14].
• Thus, morphogenetic cytokines like BMP-6 might contribute to radial glial cell function in organizing the migration of immature neurons during the development of the CNS cortex [15].
• Here we demonstrate expression of a TGF-beta-related bone morphogenetic protein, the vgr (BMP-6, DVR-6) in Schwann cells of the rat peripheral nervous system [2].

Associations of Bmp6 with chemical compounds

• The suppression of cell proliferation or glial development by the antimitotic fluorodeoxyuridine removed the effects on striatal neurons, suggesting the involvement of astroglial cells in the differentiation induced by BMP-6 [16].
• Systemic administration NS-398 caused a statistically significant reduction (P<0.05) in new bone formation (25-30%) and was associated with a statistically significant reduction in BMP-6 protein and mRNA expression (50% and 65% at P<0.05 and P<0.01, respectively) [17].
• The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats [4].
• METHODS: Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H(2)O(2) in primary cortical cultures [4].

Regulatory relationships of Bmp6

• BMP-2 and BMP-6 also inhibited BMP-4 mRNA levels [18].

Other interactions of Bmp6

• 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 [12].
• Whereas, cell bodies remained rounded in control medium or with only BMPs present, addition of BMP4 or BMP6 robustly increased the neuritogenic effect of NGF within 2 days [10].
• Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis [6].
• At 10 ng/ml and under serum-free conditions, most BMPs promoted the survival of dopaminergic neurons visualized by tyrosine hydroxylase immunocytochemistry during an 8-day culture period, but to varying extents (relative potencies: BMP 6 = 12 > 2, 4, 7) [14].
• Addition of IGF-I or BMP-6 to fetal calvaria precursor cell cultures enhanced differentiation but could not overcome TNF inhibition, suggesting that TNF acted downstream of these proteins in the differentiation pathway [19].

Analytical, diagnostic and therapeutic context of Bmp6

• By Northern blotting BMP-6-specific transcripts 3.7 kb in size were detected in major amounts in lung and in minor quantities in spleen, kidney, heart, brain, and liver [13].
• Rat BMP-6-coding cDNAs were generated by homology cloning using RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BMP-6, respectively [13].
• However, only BMP-6 could stimulate neurite outgrowth, measured with a neurofilament ELISA, an effect that was seen over the first 6 days in culture [11].
• An interstitial localization of BMP-6 was also observed in the cerebral cortex, particularly after reperfusion [3].
• In situ hybridization showed that most of the neurons possessed high levels of BMP-6 mRNA in the neonatal brain, while in the adult brain, BMP-6 mRNA level was significantly decreased in most of the neurons except those in hippocampus which retained high levels [20].

References