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01.05.2010 | Original Article

Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation

verfasst von: Ignazio Barbagallo, Angelo Vanella, Stephen J. Peterson, Dong Hyun Kim, Daniele Tibullo, Cesarina Giallongo, Luca Vanella, Nunziatina Parrinello, Giuseppe A. Palumbo, Francesco Di Raimondo, Nader G. Abraham, David Asprinio

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 3/2010

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Abstract

Human bone marrow mesenchymal stem cells (MSCs) are pleiotrophic cells that differentiate to either adipocytes or osteoblasts as a result of crosstalk by specific signaling pathways including heme oxygenase (HO)-1/-2 expression. We examined the effect of inducers of HO-1 expression and inhibitors of HO activity on MSC differentiation to the osteoblast and following high glucose exposure. MSC cultured in osteogenic medium increased expression of osteonectin, Runt-related transcription factor 2 (RUNX-2), osteocalcin, and alkaline phosphatase. HO-1 expression during differentiation was initially decreased and then followed by a rebound increase after 15 days of culture. Additionally, the effect of HO-1 on osteoblasts appears different to that seen in adipocyte stem cells. On addition of a cobalt compound, the resultant induction of HO-1 decreases adipogenesis. Moreover, glucose (30 mM) inhibited osteoblast differentiation, as evidenced by decreased bone morphogenetic protein (BMP)-2, osteonectin, osteocalcin, and osteoprotegerin (OPG). In contrast, MSC-derived adipocytes were increased by glucose. Increased HO-1 expression increased the levels of osteonectin, OPG, and BMP-2. Inhibition of HO activity prevented the increase in osteonectin and potentiated the decrease of osteocalcin and OPG in cells exposed to high glucose levels. Furthermore, targeting HO-1 expression increased pAMPK and endothelial nitric oxide synthase (eNOS) and restored osteoblastic markers. Our findings suggest that targeting HO-1 gene expression attenuates the hyperglycemia-mediated decrease in MSC-derived osteoblast differentiation. Finally, the mechanism underlying the HO-1-specific cell effect on osteoblasts and adipocytes is yet to be explored. Thus, the targeting of HO-1 gene expression presents a portal to increase osteoblast function and differentiation and attenuate osteoporosis by promoting bone formation.

Ferrari G, Cusella-De AG, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279:1528–1530CrossRefPubMed

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147CrossRefPubMed

Marie PJ, Fromigue O (2006) Osteogenic differentiation of human marrow-derived mesenchymal stem cells. Regen Med 1:539–548CrossRefPubMed

Barbagallo I, Tibullo D, Di RM, Giallongo C, Palumbo GA, Raciti G, Campisi A, Vanella A, Green CJ, Motterlini R (2008) A cytoprotective role for the heme oxygenase-1/CO pathway during neural differentiation of human mesenchymal stem cells. J Neurosci Res 86:1927–1935CrossRefPubMed

Hamilton EJ, Rakic V, Davis WA, Chubb SA, Kamber N, Prince RL, Davis TM (2009) Prevalence and predictors of osteopenia and osteoporosis in adults with type 1 diabetes. Diabet Med 26:45–52CrossRefPubMed

Fowlkes JL, Bunn RC, Liu L, Wahl EC, Coleman HN, Cockrell GE, Perrien DS, Lumpkin CK Jr, Thrailkill KM (2008) Runt-related transcription factor 2 (RUNX2) and RUNX2-related osteogenic genes are down-regulated throughout osteogenesis in type 1 diabetes mellitus. Endocrinology 149:1697–1704CrossRefPubMed

Yaturu S, Humphrey S, Landry C, Jain SK (2009) Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes. Med Sci Monit 15:CR5–CR9PubMed

Inaba M, Terada M, Koyama H, Yoshida O, Ishimura E, Kawagishi T, Okuno Y, Nishizawa Y, Otani S, Morii H (1995) Influence of high glucose on 1, 25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells. J Bone Miner Res 10:1050–1056CrossRefPubMed

Terada M, Inaba M, Yano Y, Hasuma T, Nishizawa Y, Morii H, Otani S (1998) Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells. Bone (NY) 22:17–23

10.

Bab I, Gazit D, Chorev M, Muhlrad A, Shteyer A, Greenberg Z, Namdar M, Kahn A (1992) Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity. EMBO J 11:1867–1873PubMed

11.

Li M, Kim DH, Tsenovoy PL, Peterson SJ, Rezzani R, Rodella LF, Aronow WS, Ikehara S, Abraham NG (2008) Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes 57:1526–1535CrossRefPubMed

12.

Abraham NG, Li M, Vanella L, Peterson SJ, Ikehara S, Asprinio D (2008) Bone marrow stem cell transplant into intra-bone cavity prevents type 2 diabetes: role of heme oxygenase-adiponectin. J Autoimmun 30:128–135CrossRefPubMed

13.

Abraham NG, Nelson JC, Ahmed T, Konwalinka G, Levere RD (1989) Erythropoietin controls heme metabolic enzymes in normal human bone marrow culture. Exp Hematol 17:908–913PubMed

14.

Abraham NG, Lutton JD, Levere RD (1985) Heme metabolism and erythropoiesis in abnormal iron states: role of delta-aminolevulinic acid synthase and heme oxygenase. Exp Hematol 13:838–843PubMed

15.

Abraham NG (1991) Molecular regulation: biological role of heme in hematopoiesis. Blood Rev 5:19–28CrossRefPubMed

16.

Otterbein LE, Soares MP, Yamashita K, Bach FH (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24:449–455CrossRefPubMed

17.

Chae HJ, Chin HY, Lee GY, Park HR, Yang SK, Chung HT, Pae HO, Kim HM, Chae SW, Kim HR (2006) Carbon monoxide and nitric oxide protect against tumor necrosis factor-alpha-induced apoptosis in osteoblasts: HO-1 is necessary to mediate the protection. Clin Chim Acta 365:270–278CrossRefPubMed

18.

Zwerina J, Tzima S, Hayer S, Redlich K, Hoffmann O, Hanslik-Schnabel B, Smolen JS, Kollias G, Schett G (2005) Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J 19:2011–2013PubMed

19.

Abraham NG, Kappas A (2008) Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev 60:79–127CrossRefPubMed

20.

Peterson SJ, Drummond G, Hyun KD, Li M, Kruger AL, Ikehara S, Abraham NG (2008) L-4F treatment reduces adiposity, increases adiponectin levels and improves insulin sensitivity in obese mice. J Lipid Res 49:1658–1669CrossRefPubMed

21.

Kim DH, Burgess AP, Li M, Tsenovoy PL, Addabbo F, McClung JA, Puri N, Abraham NG (2008) Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells. J Pharmacol Exp Ther 325:833–840CrossRefPubMed

22.

Li Volti G, Wang J, Traganos F, Kappas A, Abraham NG (2002) Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 296:1077–1082CrossRefPubMed

23.

Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ, Figdor CG (2003) Different faces of the heme-heme oxygenase system in inflammation. Pharmacol Rev 55:551–571CrossRefPubMed

24.

Li Volti G, Sacerdoti D, Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck JR, Abraham NG (2005) Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells. Antioxid Redox Signal 7:704–710CrossRefPubMed

25.

Deramaudt BM, Braunstein S, Remy P, Abraham NG (1998) Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem 68:121–127CrossRefPubMed

26.

Sabaawy HE, Zhang F, Nguyen X, Elhosseiny A, Nasjletti A, Schwartzman M, Dennery P, Kappas A, Abraham NG (2001) Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats. Hypertension 38:210–215PubMed

27.

Kushida T, Quan S, Yang L, Ikehara S, Kappas A, Abraham NG (2002) A significant role for the heme oxygenase-1 gene in endothelial cell cycle progression. Biochem Biophys Res Commun 291:68–75CrossRefPubMed

28.

Zhang B, Tang C, Du J (2003) Changes of heme oxygenase-carbon monoxide system in vascular calcification in rats. Life Sci 72:1027–1037CrossRefPubMed

29.

Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed

30.

Price PA (1989) Gla-containing proteins of bone. Connect Tissue Res 21:51–57CrossRefPubMed

31.

Achemlal L, Tellal S, Rkiouak F, Nouijai A, Bezza A, Derouiche EM, Ghafir D, El Maghraoui A (2005) Bone metabolism in male patients with type 2 diabetes. Clin Rheumatol 24:493–496CrossRefPubMed

32.

Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270CrossRefPubMed

33.

Armour KE, Armour KJ, Gallagher ME, Godecke A, Helfrich MH, Reid DM, Ralston SH (2001) Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 142:760–766CrossRefPubMed

34.

Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617CrossRefPubMed

35.

Garrett IR, Gutierrez G, Mundy GR (2001) Statins and bone formation. Curr Pharm Des 7:715–736CrossRefPubMed

36.

Kruger AL, Peterson SJ, Schwartzman ML, Fusco H, McClung JA, Weiss M, Shenouda S, Goodman AI, Goligorsky MS, Kappas A, Abraham NG (2006) Up-regulation of heme oxygenase provides vascular protection in an animal model of diabetes through its antioxidant and antiapoptotic effects. J Pharmacol Exp Ther 319:1144–1152CrossRefPubMed

37.

Kruger AL, Peterson S, Turkseven S, Kaminski PM, Zhang FF, Quan S, Wolin MS, Abraham NG (2005) D-4F induces heme oxygenase-1 and extracellular superoxide dismutase, decreases endothelial cell sloughing, and improves vascular reactivity in rat model of diabetes. Circulation 111:3126–3134CrossRefPubMed

38.

Hamada Y, Kitazawa S, Kitazawa R, Fujii H, Kasuga M, Fukagawa M (2007) Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: a possible role of oxidative stress. Bone (NY) 40:1408–1414

39.

Schwartz AV (2003) Diabetes mellitus: does it affect bone? Calcif Tissue Int 73:515–519CrossRefPubMed

40.

Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR (2001) Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 86:32–38CrossRefPubMed

41.

Botolin S, Faugere MC, Malluche H, Orth M, Meyer R, McCabe LR (2005) Increased bone adiposity and peroxisomal proliferator-activated receptor-gamma2 expression in type I diabetic mice. Endocrinology 146:3622–3631CrossRefPubMed

42.

Al-Mashat HA, Kandru S, Liu R, Behl Y, Desta T, Graves DT (2006) Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing. Diabetes 55:487–495CrossRefPubMed

43.

Hofbauer LC, Brueck CC, Singh SK, Dobnig H (2007) Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 22:1317–1328CrossRefPubMed

44.

Kinobe RT, Ji Y, Vlahakis JZ, Motterlini R, Brien JF, Szarek WA, Nakatsu K (2007) Effectiveness of novel imidazole-dioxolane heme oxygenase inhibitors in renal proximal tubule epithelial cells. J Pharmacol Exp Ther 323(3):763–770CrossRefPubMed

45.

Berger AJ, Itzkan I, Feld MS (1997) Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc 53A:287–292CrossRefPubMed

46.

Morigi M, Angioletti S, Imberti B, Donadelli R, Micheletti G, Figliuzzi M, Remuzzi A, Zoja C, Remuzzi G (1998) Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. J Clin Invest 101:1905–1915CrossRefPubMed

47.

Chang SH, Barbosa-Tessmann I, Chen C, Kilberg MS, Agarwal A (2002) Glucose deprivation induces heme oxygenase-1 gene expression by a pathway independent of the unfolded protein response. J Biol Chem 277:1933–1940CrossRefPubMed

48.

Quan S, Kaminski PM, Yang L, Morita T, Inaba M, Ikehara S, Goodman AI, Wolin MS, Abraham NG (2004) Heme oxygenase-1 prevents superoxide anion-associated endothelial cell sloughing in diabetic rats. Biochem Biophys Res Commun 315:509–516CrossRefPubMed

49.

Chang SH, Garcia J, Melendez JA, Kilberg MS, Agarwal A (2003) Haem oxygenase 1 gene induction by glucose deprivation is mediated by reactive oxygen species via the mitochondrial electron-transport chain. Biochem J 371:877–885CrossRefPubMed

50.

Abraham NG, Kushida T, McClung J, Weiss M, Quan S, Lafaro R, Darzynkiewicz Z, Wolin M (2003) Heme oxygenase-1 attenuates glucose-mediated cell growth arrest and apoptosis in human microvessel endothelial cells. Circ Res 93:507–514CrossRefPubMed

51.

Turkseven S, Kruger A, Mingone CJ, Kaminski P, Inaba M, Rodella LF, Ikehara S, Wolin MS, Abraham NG (2005) Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes. Am J Physiol Heart Circ Physiol 289:H701–H707CrossRefPubMed

52.

Di Noia MA, Van DS, Palmieri F, Yang LM, Quan S, Goodman AI, Abraham NG (2006) Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C oxidase activity in experimental diabetes. J Biol Chem 281:15687–15693CrossRefPubMed

53.

Schadinger SE, Bucher NL, Schreiber BM, Farmer SR (2005) PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 288:E1195–E1205CrossRefPubMed

54.

Liu J, Farmer SR (2004) Regulating the balance between peroxisome proliferator-activated receptor gamma and beta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes. J Biol Chem 279:45020–45027CrossRefPubMed

55.

Chertkov JL, Jiang S, Lutton JD, Harrison J, Levere RD, Tiefenthaler M, Abraham NG (1993) The hematopoietic stromal microenvironment promotes retrovirus-mediated gene transfer into hematopoietic stem cells. Stem Cells 11:218–227CrossRefPubMed

56.

Wagener FADTG, Feldman E, de Witte T, Abraham NG (1997) Heme induces the expression of adhesion molecules ICAM-1, VCAM-1, and E selectin in vascular endothelial cells. Proc Soc Exp Biol Med 216:456–463PubMed

57.

Durante W (2003) Heme oxygenase-1 in growth control and its clinical application to vascular disease. J Cell Physiol 195:373–382CrossRefPubMed

Titel: Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation
verfasst von: Ignazio Barbagallo
Angelo Vanella
Stephen J. Peterson
Dong Hyun Kim
Daniele Tibullo
Cesarina Giallongo
Luca Vanella
Nunziatina Parrinello
Giuseppe A. Palumbo
Francesco Di Raimondo
Nader G. Abraham
David Asprinio
Publikationsdatum: 01.05.2010
Verlag: Springer Japan
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 3/2010
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-009-0134-y

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Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation

Abstract

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Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

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