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An energetic orphan in an endocrine tissue: A revised perspective of the function of estrogen receptor-related receptor alpha in bone and cartilage

  1. Edith Bonnelye1,*,
  2. Jane E Aubin2

Article first published online: 15 JAN 2013

DOI: 10.1002/jbmr.1836

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 28, Issue 2, pages 225–233, February 2013

Additional Information

How to Cite

Bonnelye, E. and Aubin, J. E. (2013), An energetic orphan in an endocrine tissue: A revised perspective of the function of estrogen receptor-related receptor alpha in bone and cartilage. J Bone Miner Res, 28: 225–233. doi: 10.1002/jbmr.1836

Author Information

  1. 1

    INSERM-UMR1033, Lyon, France

  2. 2

    Department of Molecular Genetics, University of Toronto, Toronto, Canada

*INSERM-UMR1033, UFR de Medecine Lyon-Est, Rue Guillaume Paradin, 69 372 Lyon cedex 08, France.

Publication History

  1. Issue published online: 15 JAN 2013
  2. Article first published online: 15 JAN 2013
  3. Accepted manuscript online: 4 DEC 2012 10:35AM EST
  4. Manuscript Accepted: 14 NOV 2012
  5. Manuscript Revised: 9 NOV 2012
  6. Manuscript Received: 3 OCT 2012

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References

  • 1
    Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev. 2006;58(4):798–836.
  • 2
    Giguere V, Yang N, Segui P, Evans RM. Identification of a new class of steroid hormone receptors. Nature. 1988;331(6151):91–4.
  • 3
    Hong H, Yang L, Stallcup MR. Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem. 1999;274:22618–26.
  • 4
    Giguere V. To ERR in the estrogen pathway. Trends Endocrinol Metab. 2002;13(5):220–5.
  • 5
    Bonnelye E, Aubin JE. Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone. J Clin Endocrinol Metab. 2005;90(5):3115–21.
  • 6
    Scarpulla. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta. 2011;1813(7):1269–78.
  • 7
    Villena JA, Kralli A. ERRalpha:, a metabolic function for the oldest orphan. Trends Endocrinol Metab. 2008;19(8):269–76.
  • 8
    Giguère V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev. 2008;29(6):677–96.
  • 9
    Bonnelye E, Zirngibl RA, Jurdic P, Aubin JE. The orphan nuclear estrogen receptor-related receptor-(71) regulates cartilage formation in vitro: implication of Sox9. Endocrinology. 2007;148(3):1195–205.
  • 10
    Bonnelye ERP, Duval N, Cardelli M, Aubin JE. Estrogen receptor-related receptor-a regulation by interleukin-1b in prostaglandin E(2)- and cAMP-dependent pathways in osteoarthritic chondrocytes. Arthritis Rheum. 2011;63(8):2374–84.
    Direct Link:
  • 11
    Watt I. Osteoarthritis revisited—again! Skeletal Radiol. 2009;38(5):419–23.
  • 12
    Auld KL, Berasi SP, Liu Y, Cain M, Zhang Y, Huard C, Fukayama S, Zhang J, Choe S, Zhong W, Bhat BM, Bhat RA, Brown EL, Martinez RV. Estrogen-related receptor α regulates osteoblast differentiation via Wnt/β-catenin signaling. J Mol Endocrinol. 2012;48(2):177–91.
  • 13
    Bonnelye E, Laurin N, Jurdic P, Hart DA, Aubin JE. Estrogen receptor-related receptor-alpha (ERR-alpha) is dysregulated in inflammatory arthritis. Rheumatology (Oxford). 2008;47(12):1785–91.
  • 14
    Kawakami Y, Tsuda M, Takahashi S, Taniguchi N, Esteban CR, Zemmyo M, Furumatsu T, Lotz M, Izpisúa Belmonte JC, Asahara H. Transcriptional coactivator PGC-1alpha regulates chondrogenesis via association with Sox9. Proc Natl Acad Sci U S A. 2005;102(2):2414–9.
  • 15
    Wei W, Wang X, Yang M, Smith LC, Dechow PC, Sonoda J, Evans RM, Wan Y. PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss. Cell Metab. 2010;11(6):503–16.
  • 16
    Grey A. Thiazolidinedione-induced skeletal fragility—mechanisms and implications. Diabetes Obes Metab. 2009;11(4):275–84.
    Direct Link:
  • 17
    Bonnelye E, Saltel F, Chabadel A, Zirngibl RA, Aubin JE, Jurdic P. Involvement of the orphan nuclear estrogen receptor-related receptor a in osteoclast adhesion and transmigration. J Mol Endocrinol. 2010;45(6):365–77.
  • 18
    Destaing O, Saltel F, Geminard JC, Jurdic P, Bard F. Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol Biol Cell. 2003;14(2):407–16.
  • 19
    Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H, Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K. Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med. 2009;15(3):259–66.
  • 20
    Bonnelye E, Merdad L, Kung V, Aubin JE. The orphan nuclear estrogen receptor–related receptor (ERR) is expressed throughout osteoblast differentiation and regulates bone formation in vitro. J Cell Biol. 2001;153(5):971–83.
  • 21
    Rajalin AM, Pollock H, Aarnisalo P. ERRalpha regulates osteoblastic and adipogenic differentiation of mouse bone marrow mesenchymal stem cells. Biochem Biophys Res Commun. 2010;396(2):477–82.
  • 22
    Delhon I, Gutzwiller S, Morvan F, Rangwala S, Wyder L, Evans G, Studer A, Kneissel M, Fournier B. Absence of estrogen receptor related alpha increases osteoblastic differentiation and cancellous bone mineral density. Endocrinology. 2009;150(10):4463–72.
  • 23
    Teyssier C, Gallet M, Rabier B, Monfoulet L, Dine J, Macari C, Espallergues J, Horard B, Giguère V, Cohen-Solal M, Chassande O, Vanacker JM. Absence of ERRalpha in female mice confers resistance to bone loss induced by age or estrogen-deficiency. PLoS One. 2009 Nov 20; 4(11):e7942.
  • 24
    Bonnelye E, Kung V, Laplace C, Galson DL, Aubin JE. Estrogen receptor-related receptor alpha impinges on the estrogen axis in bone: potential function in osteoporosis. Endocrinology. 2002;143(9):3658–70.
  • 25
    Jeong BC, Lee YS, Park YY, Bae IH, Kim DK, Koo SH, Choi HR, Kim SH, Franceschi RT, Koh JT, Choi HS. The orphan nuclear receptor estrogen receptor-related receptor gamma negatively regulates BMP2-induced osteoblast differentiation and bone formation. J Biol Chem. 2009;284(21):14211–8.
  • 26
    Cardelli M, Guo R, Boetto J, Zirngibl R, Aubin J. Estrogen receptor-related receptor gamma (ERRγ) is a regulator of bone turnover [Internet]. J Bone Miner Res. 2011;26(Suppl 1):Poster Sessions, Presentation Number: SA0484. [cited 2012 Dec 2]. Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=7f807fa8-2ec2-48ed-838c-39cad1d16fdc.
  • 27
    Sanyal S, Kim JY, Kim HJ, Takeda J, Lee YK, Moore DD, Choi HS. Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms. J Biol Chem. 2002;277(3):1739–48.
  • 28
    Ondracek CR, Rushing CN, Reese VC, Oropeza CE, McLachlan A. Peroxisome proliferator-activated receptor gamma Coactivator 1alpha and small heterodimer partner differentially regulate nuclear receptor-dependent hepatitis B virus biosynthesis. J Virol. 2009;83(23):12535–44.
  • 29
    Jeong BC, Lee YS, Bae IH, Lee CH, Shin HI, Ha HJ, Franceschi RT, Choi HS, Koh JT. The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation. J Bone Miner Res. 2010;25(2):262–74.
    Direct Link:
  • 30
    Ao A, Wang H, Kamarajugadda S, Lu J. Involvement of estrogen-related receptors in transcriptional response to hypoxia and growth of solid tumors. Proc Natl Acad Sci U S A. 2008;105(22):7821–6.
  • 31
    Wan C, Gilbert SR, Wang Y, Cao X, Shen X, Ramaswamy G, Jacobsen KA, Alaql ZS, Eberhardt AW, Gerstenfeld LC, Einhorn TA, Deng L, Clemens TL. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A. 2008;105(2):686–91.
  • 32
    Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faugere MC, Guldberg RE, Gerstenfeld LC, Haase VH, Johnson RS, Schipani E, Clemens TL. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007;117(6):1616–26.
  • 33
    Knowles HJ, Cleton-Jansen AM, Korsching E, Athanasou NA. Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4. FASEB J. 2010;24(12):4648–59.
  • 34
    Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature. 2008;451(7181):1008–12.
  • 35
    Stein RA, Gaillard S, McDonnell DP. Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells. J Steroid Biochem Mol Biol. 2009;114(1–2):106–12.
  • 36
    Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguere V. Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha. Mol Cell Biol. 2003;23(22):7947–56.
  • 37
    Naot D, Chhana A, Matthews BG, Callon KE, Tong PC, Lin JM, Costa JL, Watson M, Grey AB, Cornish J. Molecular mechanisms involved in the mitogenic effect of lactoferrin in osteoblasts. Bone. 2011 Aug; 49(2):217–24.
  • 38
    Zelzer E, Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol. 2005;65:169–87.
  • 39
    Chang CY, Kazmin D, Jasper JS, Kunder R, Zuercher WJ, McDonnell DP. The metabolic regulator ERRa, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer. Cancer Cell. 2011;20(4):500–10.
  • 40
    Klinge CM, Kaur K, Swanson HI. The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1. Arch Biochem Biophys. 2000;373(1):163–74.
  • 41
    Ryan EP, Holz JD, Mulcahey M, Sheu TJ, Gasiewicz TA, Puzas JE. Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. J Bone Miner Res. 2007;22(10):1571–80.
    Direct Link:
  • 42
    Wejheden C, Brunnberg S, Larsson S, Lind PM, Andersson G, Hanberg A. Transgenic mice with a constitutively active aryl hydrocarbon receptor display a gender-specific bone phenotype. Toxicol Sci. 2012;114(1):48–58.
  • 43
    Sharan K, Mishra JS, Swarnkar G, Siddiqui JA, Khan K, Kumari R, Rawat P, Maurya R, Sanyal S, Chattopadhyay N. A novel quercetin analogue from a medicinal plant promotes peak bone mass achievement and bone healing after injury and exerts an anabolic effect on osteoporotic bone: the role of aryl hydrocarbon receptor as a mediator of osteogenic action. J Bone Miner Res. 2011;26(9):2096–111.
    Direct Link:
  • 44
    Huss JM, Torra IP, Staels B, Giguere V, Kelly DP. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 2004;24(20):9079–91.
  • 45
    Stunes AK, Westbroek I, Gustafsson BI, Fossmark R, Waarsing JH, Eriksen EF, Petzold C, Reseland JE, Syversen U. The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats. BMC Endocr Disord. 2011;11:11.
  • 46
    Syversen U, Stunes AK, Gustafsson BI, Obrant KJ, Nordsletten L, Berge R, Thommesen L, Reseland JE. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord. 2009;9:10.
  • 47
    Sekiya I, Vuoristo JT, Larson BL, Prockop DJ. In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Proc Natl Acad Sci U S A. 2002;99(7):4397–402.
  • 48
    Friedman MS, Oyserman SM, Hankenson KD. Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2. J Biol Chem. 2009;284(21):14117–25.
  • 49
    Dwyer MA, Joseph JD, Wade HE, Eaton ML, Kunder RS, Kazmin D, Chang CY, McDonnell DP. WNT11 expression is induced by estrogen-related receptor alpha and beta-catenin and acts in an autocrine manner to increase cancer cell migration. Cancer Res. 2010 Nov 15; 70(22):9298–308.
  • 50
    Fradet A, Sorel H, Bouazza L, Goehrig D, Dépalle B, Bellahcène A, Castronovo V, Follet H, Descotes F, Aubin JE, Clézardin P, Bonnelye E. Dual function of ERRalpha in breast cancer and bone metastases formation: implication of VEGF and osteoprotegerin. Cancer Res. 2011;71(17):5728–38.
  • 51
    Sladek R, Bader JA, Giguere V. The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene. Mol Cell Biol. 1997;17(9):5400–9.
  • 52
    Vega RB, Kelly DP. A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. J Biol Chem. 1997;272(50):31693–9.
  • 53
    Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A. 2004;101(17):6570–5.
  • 54
    Wende AR, Huss JM, Schaeffer PJ, Giguère V, Kelly DP. PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol. 2005;25(24):10684–94.
  • 55
    Nie Y, Wong C. Suppressing the activity of ERRalpha in 3T3-L1 adipocytes reduces mitochondrial biogenesis but enhances glycolysis and basal glucose uptake. J Cell Mol Med. 2009;13(9B):3051–60.
    Direct Link:
  • 56
    Zhang Y, Ma K, Sadana P, Chowdhury F, Gaillard S, Wang F, McDonnell DP, Unterman TG, Elam MB, Park EA. Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. J Biol Chem. 2006;281(52):39897–06.
  • 57
    Connaughton S, Chowdhury F, Attia RR, Song S, Zhang Y, Elam MB, Cook GA, Park EA. Regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) gene expression by glucocorticoids and insulin. Mol Cell Endocrinol. 2010;315(1–2):159–67.
  • 58
    Araki M, Motojima K. Identification of ERRalpha as a specific partner of PGC-1alpha for the activation of PDK4 gene expression in muscle. FEBS J. 2006;273(8):1669–80.
    Direct Link:
  • 59
    Herzog B, Cardenas J, Hall RK, Villena JA, Budge PJ, Giguère V, Granner DK, Kralli A. Estrogen-related receptor alpha is a repressor of phosphoenolpyruvate carboxykinase gene transcription. J Biol Chem. 2006;281(1):99–106.
  • 60
    Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008;105(13):5266–70.
  • 61
    Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.
  • 62
    Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature. 2012;481(7381):314–20.
  • 63
    Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone. 2012;50(2):568–75.
  • 64
    Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Brüning JC, Clemens TL. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142(2):309–19.
  • 65
    Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Myers MG Jr, Chua SC Jr, Kim JK, Kaestner KH, Karsenty G. The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. J Cell Biol. 2008;183(7):1235–42.
  • 66
    Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Kajimura D, Myers MG Jr, Chua SC Jr, Wang Q, Kim JK, Kaestner KH, Karsenty G. An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion. Ann N Y Acad Sci. 2009 Sep; 1173(Suppl 1):E20–30.
    Direct Link:
  • 67
    Takeda S. [Control of bone metabolism by central nervous system]. Clin Calcium. 2011;21(5):691–6. Japanese.
  • 68
    Ijichi N, Ikeda K, Horie-Inoue K, Yagi K, Okazaki Y, Inoue S. Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation. Biochem Biophys Res Commun. 2007;358(3):813–8.
  • 69
    Ju D, He J, Zhao L, Zheng X, Yang G. Estrogen related receptor α-induced adipogenesis is PGC-1β-dependent. Mol Biol Rep. 2012;39(3):3343–54.
  • 70
    Tremblay AM, Dufour CR, Ghahremani M, Reudelhuber TL, Giguère V. Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway. Mol Endocrinol. 2010;24(1):22–32.
  • 71
    Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005;102(15):5618–23.
  • 72
    Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300(5622):1140–2.
  • 73
    Anderson R, Prolla T. PGC-1alpha in aging and anti-aging interventions. Biochim Biophys Acta. 2009;1790(10):1059–66.
  • 74
    Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2(3):165–71.
  • 75
    Almeida M, Ambrogini E, Han L, Manolagas SC, Jilka RL. Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic Wnt signaling in the skeleton. J Biol Chem. 2009;284(40):27438–48.
  • 76
    Almeida M. Unraveling the role of FoxOs in bone—insights from mouse models. Bone. 2011;49(3):319–27.
  • 77
    Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31(3):266–300.
  • 78
    Kousteni S. FoxOs: Unifying links between oxidative stress and skeletal homeostasis. Curr Osteoporos Rep. 2011;9(2):60–6.
  • 79
    Rached MT, Kode A, Silva BC, Jung DY, Gray S, Ong H, Paik JH, DePinho RA, Kim JK, Karsenty G, Kousteni S. FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice. J Clin Invest. 2010;120(1):357–68.
  • 80
    Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest. 1990;85(3):632–9.
  • 81
    Lee DH, Lim BS, Lee YK, Yang HC. Effects of hydrogen peroxide (H2O2) on alkaline phosphatase activity and matrix mineralization of odontoblast and osteoblast cell lines. Cell Biol Toxicol. 2006;22(1):39–46.
  • 82
    Wang J, Wang Y, Wong C. Oestrogen-related receptor alpha inverse agonist XCT-790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production. Cell Prolif. 2010;43(2):103–13.
    Direct Link:
  • 83
    Chen L, Wong C. Estrogen-related receptor alpha inverse agonist enhances basal glucose uptake in myotubes through reactive oxygen species. Biol Pharm Bull. 2009;32(7):1199–203.
  • 84
    Wang Y, Fang F, Wong CW. Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010;80(1):80–5.
  • 85
    Sonoda J, Laganière J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, Lee CH, Giguère V, Evans RM. Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev. 2007;21(15):1909–20.
  • 86
    Rangwala SM, Li X, Lindsley L, Wang X, Shaughnessy S, Daniels TG, Szustakowski J, Nirmala NR, Wu Z, Stevenson SC. Estrogen-related receptor alpha is essential for the expression of antioxidant protection genes and mitochondrial function. Biochem Biophys Res Commun. 2007;357(1):231–6.
  • 87
    Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F, Chang Y. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One. 2010;5(7):e11707.
  • 88
    Gallet M, Vanacker JM. ERR receptors as potential targets in osteoporosis. Trends Endocrinol Metab. 2010;21(10):637–41.
  • 89
    Zirngibl RA, Chan JS, Aubin JE. Estrogen receptor-related receptor alpha (ERRalpha) regulates osteopontin expression through a non-canonical ERRalpha response element in a cell context-dependent manner. J Mol Endocrinol. 2008;40(2):61–73.
  • 90
    Vanacker JM, Bonnelye E, Delmarre C, Laudet V. Oncogene. 2008;17(19):2429–2435.
  • 91
    Yang C, Zhou D, Chen S. Modulation of aromatase expression in the breast tissue by ERR alpha-1 orphan receptor. Cancer Res. 1998;58(24):5695–700.
  • 92
    Yang C, Yu B, Zhou D, Chen S. Regulation of aromatase promoter activity in human breast tissue by nuclear receptors. Oncogene. 2002;21(18):2854–63.
  • 93
    Sumi D, Ignarro LJ. Estrogen-related receptor alpha 1 up-regulates endothelial nitric oxide synthase expression. Proc Natl Acad Sci U S A. 2003;100(24):14451–6.
  • 94
    Yang N, Shigeta H, Shi H, Teng CT. Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter. J Biol Chem. 1996;271(10):5795–804.
  • 95
    Zhang Z, Teng CT. Estrogen receptor-related receptor alpha 1 interacts with coactivator and constitutively activates the estrogen response elements of the human lactoferrin gene. J Biol Chem. 2000;275(27):20837–46.
  • 96
    Cornish J, Naot D. Lactoferrin as an effector molecule in the skeleton. Biometals. 2010;23(3):425–30.
  • 97
    Liu Y, Berendsen AD, Jia S, Lotinun S, Baron R, Ferrara N, Olsen BR. Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Invest. 2012;122(4):3101–13.
  • 98
    Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, Bouillon R, Carmeliet G. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest. 2004;113(2):188–99.
  • 99
    Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater. 2008;15:100–14.
  • 100
    Lehtinen MK, Bonni A. Modeling oxidative stress in the central nervous system. Curr Mol Med. 2006 Dec; 6(8):871–81.
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