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Gene Review

Bmp6  -  bone morphogenetic protein 6

Rattus norvegicus

Synonyms: BMP-6, Bmp-6, Bone morphogenetic protein 6, VG-1-related protein, VGR-1, ...
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Disease relevance of Bmp6


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


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


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].


  1. Bone morphogenetic proteins (BMP6 and BMP7) enhance the protective effect of neurotrophins on cultured septal cholinergic neurons during hypoglycemia. Nonner, D., Barrett, E.F., Kaplan, P., Barrett, J.N. J. Neurochem. (2001) [Pubmed]
  2. 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. Schluesener, H.J., Meyermann, R., Jung, S. Glia (1995) [Pubmed]
  3. Expression of bone morphogenetic protein-6 and transforming growth factor-beta1 in the rat brain after a mild and reversible ischemic damage. Martinez, G., Carnazza, M.L., Di Giacomo, C., Sorrenti, V., Vanella, A. Brain Res. (2001) [Pubmed]
  4. Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. Wang, Y., Chang, C.F., Morales, M., Chou, J., Chen, H.L., Chiang, Y.H., Lin, S.Z., Cadet, J.L., Deng, X., Wang, J.Y., Chen, S.Y., Kaplan, P.L., Hoffer, B.J. Stroke (2001) [Pubmed]
  5. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. Otsuka, F., Moore, R.K., Shimasaki, S. J. Biol. Chem. (2001) [Pubmed]
  6. 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. Sato, M., Ochi, T., Nakase, T., Hirota, S., Kitamura, Y., Nomura, S., Yasui, N. J. Bone Miner. Res. (1999) [Pubmed]
  7. Osteogenic protein-1 differentially regulates the mRNA expression of bone morphogenetic proteins and their receptors in primary cultures of osteoblasts. Yeh, L.C., Unda, R., Lee, J.C. J. Cell. Physiol. (2000) [Pubmed]
  8. Depolarization differentially regulates the effects of bone morphogenetic protein (BMP)-2, BMP-6, and activin A on sympathetic neuronal phenotype. Fann, M.J., Patterson, P.H. J. Neurochem. (1994) [Pubmed]
  9. Differential regulation of distinct phenotypic features of serotonergic neurons by bone morphogenetic proteins. Galter, D., Böttner, M., Krieglstein, K., Schömig, E., Unsicker, K. Eur. J. Neurosci. (1999) [Pubmed]
  10. Bone morphogenetic protein signalling in NGF-stimulated PC12 cells. Althini, S., Usoskin, D., Kylberg, A., ten Dijke, P., Ebendal, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  11. Bone morphogenetic proteins BMP-6 and BMP-7 have differential effects on survival and neurite outgrowth of cerebellar granule cell neurons. Yabe, T., Samuels, I., Schwartz, J.P. J. Neurosci. Res. (2002) [Pubmed]
  12. The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. Hughes, F.J., Collyer, J., Stanfield, M., Goodman, S.A. Endocrinology (1995) [Pubmed]
  13. Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1. Knittel, T., Fellmer, P., Müller, L., Ramadori, G. Exp. Cell Res. (1997) [Pubmed]
  14. Bone morphogenetic proteins: neurotrophic roles for midbrain dopaminergic neurons and implications of astroglial cells. Jordan, J., Böttner, M., Schluesener, H.J., Unsicker, K., Krieglstein, K. Eur. J. Neurosci. (1997) [Pubmed]
  15. Expression of BMP-6, a TGF-beta related morphogenetic cytokine, in rat radial glial cells. Schluesener, H.J., Meyermann, R. Glia (1994) [Pubmed]
  16. Bone morphogenetic protein-6 is a neurotrophic factor for calbindin-positive striatal neurons. Gratacòs, E., Gavaldà, N., Alberch, J. J. Neurosci. Res. (2002) [Pubmed]
  17. Cyclooxygenase-2 inhibition selectively attenuates bone morphogenetic protein-6 synthesis and bone formation during guided tissue regeneration in a rat model. Damrongsri, D., Geva, S., Salvi, G.E., Williams, R.C., Limwongse, V., Offenbacher, S. Clinical oral implants research. (2006) [Pubmed]
  18. Bone morphogenetic protein-4 regulates its own expression in cultured osteoblasts. Pereira, R.C., Rydziel, S., Canalis, E. J. Cell. Physiol. (2000) [Pubmed]
  19. Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Gilbert, L., He, X., Farmer, P., Boden, S., Kozlowski, M., Rubin, J., Nanes, M.S. Endocrinology (2000) [Pubmed]
  20. Developmental alteration and neuron-specific expression of bone morphogenetic protein-6 (BMP-6) mRNA in rodent brain. Tomizawa, K., Matsui, H., Kondo, E., Miyamoto, K., Tokuda, M., Itano, T., Nagahata, S., Akagi, T., Hatase, O. Brain Res. Mol. Brain Res. (1995) [Pubmed]
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