Abstract
Cytochromes P450 (CYPs) are important for bone homeostasis, but only limited information is available on their expression in human bone cells. We analyzed the expression levels of eight CYPs in osteoblasts cultured in human bone pieces, in osteoblasts differentiated from human periosteum mesenchymal stem cells, in primary human osteoblasts and in the human osteoblast cell line MG63, respectively. Our results confirm previous reports about the presence of CYP11A1, CYP17A1, CYP24A1 and CYP27B1, while demonstrating expression of CYP2E1, CYP26A1, CYP39A1 and CYP51A1 for the first time. However, expression patterns in the four models were remarkably different from each other.
Acknowledgments
The authors thank Jolanda M.A. Hogervorst from the Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU Amsterdam, and Inge Van Hoven from the Skeletal Biology and Engineering Research Center, KU Leuven, Belgium, for providing technical support.
References
Auchus, R.J. (2017). Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J. Steroid Biochem. Mol. Biol. 165, 71–78.10.1016/j.jsbmb.2016.02.002Suche in Google Scholar
Balmer, J.E. and Blomhoff, R. (2002). Gene expression regulation by retinoic acid. J. Lipid Res. 43, 1773–1808.10.1194/jlr.R100015-JLR200Suche in Google Scholar
Bernhardt, R. (2005). Cytochromes P-450. In: Encyclopedia of Biological Chemistry, W. Lennarz, M. Lane, P. Modrich, J. Dixon, E. Carafoli, J. Exton, and D. Cleveland, eds. (Cambridge, MA: Academic Press), pp. 544–549.Suche in Google Scholar
Bernhardt, R. and Urlacher, V.B. (2014). Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations. Appl. Microbiol. Biotechnol. 98, 6185–6203.10.1007/s00253-014-5767-7Suche in Google Scholar
Broulik, P.D., Vondrova, J., Ruzicka, P., Sedlacek, R., and Zima, T. (2010). The effect of chronic alcohol administration on bone mineral content and bone strength in male rats. Physiol. Res. 59, 599–604.10.33549/physiolres.931799Suche in Google Scholar
Carpenter, T.O. (2017). CYP24A1 loss of function: clinical phenotype of monoallelic and biallelic mutations. J. Steroid Biochem. Mol. Biol. doi: 10.1016/j.jsbmb.2017.01.006. [Epub ahead of print].Suche in Google Scholar
Chen, J.R., Haley, R.L., Hidestrand, M., Shankar, K., Liu, X., Lumpkin, C.K., Simpson, P.M., Badger, T.M., and Ronis, M.J. (2006). Estradiol protects against ethanol-induced bone loss by inhibiting up-regulation of receptor activator of nuclear factor-κB ligand in osteoblasts. J. Pharmacol. Exp. Ther. 319, 1182–1190.10.1124/jpet.106.109454Suche in Google Scholar
Chien, Y., Rosal, K., and Chung, B.C. (2017). Function of CYP11A1 in the mitochondria. Mol. Cell Endocrinol. 441, 55–61.10.1016/j.mce.2016.10.030Suche in Google Scholar
Czekanska, E.M., Stoddart, M.J., Richards, R.G., and Hayes, J.S. (2012). In search of an osteoblast cell model for in vitro research. Eur. Cell Mater. 24, 1–17.10.22203/eCM.v024a01Suche in Google Scholar
Dauber, A., Nguyen, T.T., Sochett, E., Cole, D.E., Horst, R., Abrams, S.A., Carpenter, T.O., and Hirschhorn, J.N. (2012). Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J. Clin. Endocrinol. Metab. 97, E268–274.10.1210/jc.2011-1972Suche in Google Scholar
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A.L., and Karsenty, G. (1997). Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89, 747–754.10.1016/S0092-8674(00)80257-3Suche in Google Scholar
Ekstrom, G. and Ingelman-Sundberg, M. (1989). Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem. Pharmacol. 38, 1313–1319.10.1016/0006-2952(89)90338-9Suche in Google Scholar
Enjuanes, A., Garcia-Giralt, N., Supervia, A., Nogues, X., Ruiz-Gaspa, S., Bustamante, M., Mellibovsky, L., Grinberg, D., Balcells, S., and Diez-Perez, A. (2005). Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation. Eur. J. Endocrinol. 153, 981–988.10.1530/eje.1.02032Suche in Google Scholar
Gennari, L., Nuti, R., and Bilezikian, J.P. (2004). Aromatase activity and bone homeostasis in men. J. Clin. Endocrinol. Metab. 89, 5898–5907.10.1210/jc.2004-1717Suche in Google Scholar
Gorsky, L.D., Koop, D.R., and Coon, M.J. (1984). On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J. Biol. Chem. 259, 6812–6817.10.1016/S0021-9258(17)39800-9Suche in Google Scholar
Guengerich, F.P. (2001a). Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14, 611–650.10.1021/tx0002583Suche in Google Scholar PubMed
Guengerich, F.P. (2001b). Uncommon P450-catalyzed reactions. Curr. Drug. Metab. 2, 93–115.10.2174/1389200013338694Suche in Google Scholar PubMed
Guengerich, F.P. (2017). Intersection of the roles of cytochrome P450 enzymes with xenobiotic and endogenous substrates: relevance to toxicity and drug interactions. Chem. Res. Toxicol. 30, 2–12.10.1021/acs.chemrestox.6b00226Suche in Google Scholar PubMed PubMed Central
Hannemann, F., Bichet, A., Ewen, K.M., and Bernhardt, R. (2007). Cytochrome P450 systems-biological variations of electron transport chains. Biochim. Biophys. Acta. 1770, 330–344.10.1016/j.bbagen.2006.07.017Suche in Google Scholar PubMed
Hodges, V.M., Molloy, G.Y., and Wickramasinghe, S.N. (2000). Demonstration of mRNA for five species of cytochrome P450 in human bone marrow, bone marrow-derived macrophages and human haemopoietic cell lines. Br. J. Haematol. 108, 151–156.10.1046/j.1365-2141.2000.01816.xSuche in Google Scholar PubMed
Holick, M.F. (2017). The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev. Endocr. Metab. Disord. 18, 153–165.10.1007/s11154-017-9424-1Suche in Google Scholar PubMed
Huang, N., Pandey, A.V., Agrawal, V., Reardon, W., Lapunzina, P.D., Mowat, D., Jabs, E.W., Van Vliet, G., Sack, J., Fluck, C.E., et al. (2005). Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am. J. Hum. Genet. 76, 729–749.10.1086/429417Suche in Google Scholar
Janssen, J.M.M.F., Bland, R., Hewison, M., Coughtrie, M.W.H., Sharp, S., Arts, J., Pols, H.A. P., and van Leeuwen, J.P.T.M. (1999). Estradiol formation by human osteoblasts via multiple pathways: Relation with osteoblast function. J. Cell Biochem. 75, 528–537.10.1002/(SICI)1097-4644(19991201)75:3<528::AID-JCB16>3.0.CO;2-3Suche in Google Scholar
Karner, C.M. and Long, F. (2017). Wnt signaling and cellular metabolism in osteoblasts. Cell Mol. Life Sci. 74, 1649–1657.10.1007/s00018-016-2425-5Suche in Google Scholar
Keber, R., Motaln, H., Wagner, K. D., Debeljak, N., Rassoulzadegan, M., Acimovic, J., Rozman, D., and Horvat, S. (2011). Mouse knockout of the cholesterogenic cytochrome P450 lanosterol 14alpha-demethylase (Cyp51) resembles Antley-Bixler syndrome. J. Biol. Chem. 286, 29086–29097.10.1074/jbc.M111.253245Suche in Google Scholar
Kung, A.W.C. (2003). Androgen and bone mass in men. Asian J. Androl. 5, 148–154.Suche in Google Scholar
Lepetsos, P. and Papavassiliou, A.G. (2016). ROS/oxidative stress signaling in osteoarthritis. Biochim. Biophys. Acta. 1862, 576–591.10.1016/j.bbadis.2016.01.003Suche in Google Scholar
Leung, T.M. and Nieto, N. (2013). CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J. Hepatol. 58, 395–398.10.1016/j.jhep.2012.08.018Suche in Google Scholar
Lewis, D.F.V. and Ito, Y. (2008) Cytochrome P450 structure and function: an evolutionary perspective. In: Cytochromes P450: Role in the Metabolism and Toxicity of Drugs and other Xenobiotics, C. Ioannides, ed. (Cambridge, UK: RSC Publishing), pp. 3–45.10.1039/9781847558428-00003Suche in Google Scholar
Lips, P. and van Schoor, N.M. (2011). The effect of vitamin D on bone and osteoporosis. Best Pract. Res. Clin. Endocrinol. Metab. 25, 585–591.10.1016/j.beem.2011.05.002Suche in Google Scholar
Lorbek, G., Lewinska, M., and Rozman, D. (2012). Cytochrome P450s in the synthesis of cholesterol and bile acids–from mouse models to human diseases. FEBS J. 279, 1516–1533.10.1111/j.1742-4658.2011.08432.xSuche in Google Scholar
Moorthy, B. (2008) The CYP1A subfamily. In: Cytochromes P450, C. Ioannides, ed. (Cambridge, UK: Royal Society of Chemistry), pp. 97–135.10.1039/9781847558428-00097Suche in Google Scholar
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z.P., Deng, J.M., Behringer, R.R., and de Crombrugghe, B. (2002). The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108, 17–29.10.1016/S0092-8674(01)00622-5Suche in Google Scholar
Nebert, D.W., Wikvall, K., and Miller, W.L. (2013). Human cytochromes P450 in health and disease. Phil. Trans. R. Soc. Lond. B. Biol. Sci. 368, 20120431.10.1098/rstb.2012.0431Suche in Google Scholar
Neunzig, J., Milhim, M., Schiffer, L., Khatri, Y., Zapp, J., Sanchez-Guijo, A., Hartmann, M.F., Wudy, S.A., and Bernhardt, R. (2017). The steroid metabolite 16β-OH-androstenedione generated by CYP21A2 serves as a substrate for CYP19A1. J. Steroid Biochem. Mol. Biol. 167, 182–191.10.1016/j.jsbmb.2017.01.002Suche in Google Scholar
Notelovitz, M. (2002). Androgen effects on bone and muscle. Fertil. Steril. 77, S34–S41.10.1016/S0015-0282(02)02968-0Suche in Google Scholar
Panda, S., Kellogg, D., Tang, K.J., and Masters, B.S. (2015). Cytochrome P450 expression revealed in long bone growth plates. FASEB J. 29, Supplement 884.63.10.1096/fasebj.29.1_supplement.884.63Suche in Google Scholar
Panda, S.P., Guntur, A.R., Polusani, S.R., Fajardo, R.J., Gakunga, P.T., Roman, L.J., and Masters, B.S. (2013). Conditional deletion of cytochrome P450 reductase in osteoprogenitor cells affects long bone and skull development in mice recapitulating Antley-Bixler syndrome: role of a redox enzyme in development. PloS One 8, e75638.10.1371/journal.pone.0075638Suche in Google Scholar PubMed PubMed Central
Parr, M.K., Zollner, A., Fussholler, G., Opfermann, G., Schlorer, N., Zorio, M., Bureik, M., and Schanzer, W. (2012). Unexpected contribution of cytochrome P450 enzymes CYP11B2 and CYP21, as well as CYP3A4 in xenobiotic androgen elimination – insights from metandienone metabolism. Toxicol. Lett. 213, 381–391.10.1016/j.toxlet.2012.07.020Suche in Google Scholar PubMed
Rittle, J. and Green, M.T. (2010). Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330, 933–937.10.1126/science.1193478Suche in Google Scholar PubMed
Rodriguez-Sanz, M., Garcia-Giralt, N., Prieto-Alhambra, D., Servitja, S., Balcells, S., Pecorelli, R., Diez-Perez, A., Grinberg, D., Tusquets, I., and Nogues, X. (2015). CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss. J. Mol. Endocrinol. 55, 69–79.10.1530/JME-15-0079Suche in Google Scholar PubMed
Schiffer, L., Brixius-Anderko, S., Hannemann, F., Zapp, J., Neunzig, J., Thevis, M., and Bernhardt, R. (2016). Metabolism of oral turinabol by human steroid hormone-synthesizing cytochrome P450 enzymes. Drug. Metab. Dispos. 44, 227–237.10.1124/dmd.115.066829Suche in Google Scholar PubMed
Teplyuk, N.M., Zhang, Y., Lou, Y., Hawse, J.R., Hassan, M.Q., Teplyuk, V.I., Pratap, J., Galindo, M., Stein, J.L., Stein, G.S., et al. (2009). The osteogenic transcription factor runx2 controls genes involved in sterol/steroid metabolism, including CYP11A1 in osteoblasts. Mol. Endocrinol. 23, 849–861.10.1210/me.2008-0270Suche in Google Scholar
Valentine, J.L., Lee, S.S., Seaton, M.J., Asgharian, B., Farris, G., Corton, J.C., Gonzalez, F.J., and Medinsky, M.A. (1996). Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression. Toxicol. Appl. Pharmacol. 141, 205–213.10.1016/S0041-008X(96)80026-3Suche in Google Scholar
van der Meijden, K., Lips, P., van Driel, M., Heijboer, A.C., Schulten, E.A., den Heijer, M., and Bravenboer, N. (2014). Primary human osteoblasts in response to 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3. PLoS One 9, e110283.10.1371/journal.pone.0110283Suche in Google Scholar PubMed PubMed Central
van Driel, M., Koedam, M., Buurman, C. J., Roelse, M., Weyts, F., Chiba, H., Uitterlinden, A. G., Pols, H.A., and van Leeuwen, J.P. (2006). Evidence that both 1α,25-dihydroxyvitamin D3 and 24-hydroxylated D3 enhance human osteoblast differentiation and mineralization. J . Cell. Biochem. 99, 922–935.10.1002/jcb.20875Suche in Google Scholar PubMed
Zöllner, A., Parr, M.K., Dragan, C.A., Dras, S., Schlorer, N., Peters, F.T., Maurer, H.H., Schanzer, W., and Bureik, M. (2010). CYP21-catalyzed production of the long-term urinary metandienone metabolite 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping. Biol. Chem. 391, 119–127.10.1515/bc.2010.002Suche in Google Scholar PubMed
Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0205).
©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
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Artikel in diesem Heft
- Frontmatter
- Reviews
- Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology
- Cystine knot growth factors and their functionally versatile proregions
- Kallistatin: double-edged role in angiogenesis, apoptosis and oxidative stress
- Minireview
- The sphingomyelin synthase family: proteins, diseases, and inhibitors
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Comparison of cytochrome P450 expression in four different human osteoblast models
- Cell Biology and Signaling
- The molecular mechanisms involved in lectin-induced human platelet aggregation
- HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8
- Heat shock protein 47 effects on hepatic stellate cell-associated receptors in hepatic fibrosis of Schistosoma japonicum-infected mice