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Published in: Calcified Tissue International 2/2014

Open Access 01-08-2014 | Original Research

Impact of Dietary Aromatic Amino Acids on Osteoclastic Activity

Authors: Mona El Refaey, Qing Zhong, Ke-Hong Ding, Xing-ming Shi, Jianrui Xu, Wendy B. Bollag, William D. Hill, Norman Chutkan, Richard Robbins, Hugh Nadeau, Maribeth Johnson, Mark W. Hamrick, Carlos M. Isales

Published in: Calcified Tissue International | Issue 2/2014

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Abstract

We had shown that aromatic amino acid (phenylalanine, tyrosine, and tryptophan) supplementation prevented bone loss in an aging C57BL/6 mice model. In vivo results from the markers of bone breakdown suggested an inhibition of osteoclastic activity or differentiation. To assess osteoclastic differentiation, we examined the effects of aromatic amino acids on early /structural markers as vitronectin receptor, calcitonin receptor, and carbonic anhydrase II as well as, late/functional differentiation markers; cathepsin K and matrix metalloproteinase 9 (MMP-9). Our data demonstrate that the aromatic amino acids down-regulated early and late osteoclastic differentiation markers as measured by real time PCR. Our data also suggest a link between the vitronectin receptor and the secreted cathepsin K that both showed consistent effects to the aromatic amino acid treatment. However, the non-attachment related proteins, calcitonin receptor, and carbonic anhydrase II, demonstrated less consistent effects in response to treatment. Our data are consistent with aromatic amino acids down-regulating osteoclastic differentiation by suppressing remodeling gene expression thus contributing initially to the net increase in bone mass seen in vivo.
Literature
1.
go back to reference Rasschaert J, Malaisse WJ (1999) Expression of the calcium-sensing receptor in pancreatic islet B-cells. Biochem Biophys Res Commun 264:615–618PubMedCrossRef Rasschaert J, Malaisse WJ (1999) Expression of the calcium-sensing receptor in pancreatic islet B-cells. Biochem Biophys Res Commun 264:615–618PubMedCrossRef
2.
go back to reference House MG, Kohlmeier L, Chattopadhyay N, Kifor O, Yamaguchi T et al (1997) Expression of an extracellular calcium-sensing receptor in human and mouse bone marrow cells. J Bone Miner Res 12:1959–1970PubMedCrossRef House MG, Kohlmeier L, Chattopadhyay N, Kifor O, Yamaguchi T et al (1997) Expression of an extracellular calcium-sensing receptor in human and mouse bone marrow cells. J Bone Miner Res 12:1959–1970PubMedCrossRef
4.
go back to reference Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA et al (2004) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol 164:509–514PubMedCentralPubMedCrossRef Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA et al (2004) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol 164:509–514PubMedCentralPubMedCrossRef
5.
go back to reference Turner AG, Tjahyono F, Chiu WS, Skinner J, Sawyer R et al (2011) The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption. Bone 48:354–361PubMedCrossRef Turner AG, Tjahyono F, Chiu WS, Skinner J, Sawyer R et al (2011) The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption. Bone 48:354–361PubMedCrossRef
6.
go back to reference Felix R, Hofstetter W, Cecchini MG (1996) Recent developments in the understanding of the pathophysiology of osteopetrosis. Eur J Endocrinol 134:143–156PubMedCrossRef Felix R, Hofstetter W, Cecchini MG (1996) Recent developments in the understanding of the pathophysiology of osteopetrosis. Eur J Endocrinol 134:143–156PubMedCrossRef
7.
go back to reference Lehenkari P, Hentunen TA, Laitala-Leinonen T, Tuukkanen J, Vaananen HK (1998) Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+. Exp Cell Res 242:128–137PubMedCrossRef Lehenkari P, Hentunen TA, Laitala-Leinonen T, Tuukkanen J, Vaananen HK (1998) Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+. Exp Cell Res 242:128–137PubMedCrossRef
8.
go back to reference Andersen TL, del Carmen Ovejero M, Kirkegaard T, Lenhard T, Foged NT et al (2004) A scrutiny of matrix metalloproteinases in osteoclasts: evidence for heterogeneity and for the presence of MMPs synthesized by other cells. Bone 35:1107–1119PubMedCrossRef Andersen TL, del Carmen Ovejero M, Kirkegaard T, Lenhard T, Foged NT et al (2004) A scrutiny of matrix metalloproteinases in osteoclasts: evidence for heterogeneity and for the presence of MMPs synthesized by other cells. Bone 35:1107–1119PubMedCrossRef
9.
go back to reference Galliera E, Randelli P, Dogliotti G, Dozio E, Colombini A et al (2010) Matrix metalloproteases MMP-2 and MMP-9: are they early biomarkers of bone remodelling and healing after arthroscopic acromioplasty? Injury 41:1204–1207PubMedCrossRef Galliera E, Randelli P, Dogliotti G, Dozio E, Colombini A et al (2010) Matrix metalloproteases MMP-2 and MMP-9: are they early biomarkers of bone remodelling and healing after arthroscopic acromioplasty? Injury 41:1204–1207PubMedCrossRef
10.
go back to reference Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA et al (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93:411–422PubMedCentralPubMedCrossRef Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA et al (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93:411–422PubMedCentralPubMedCrossRef
11.
go back to reference Drake FH, Dodds RA, James IE, Connor JR, Debouck C et al (1996) Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem 271:12511–12516PubMedCrossRef Drake FH, Dodds RA, James IE, Connor JR, Debouck C et al (1996) Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem 271:12511–12516PubMedCrossRef
12.
go back to reference Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH et al (1998) The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 273:32347–32352PubMedCrossRef Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH et al (1998) The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 273:32347–32352PubMedCrossRef
13.
go back to reference Bossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR et al (1996) Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem 271:12517–12524PubMedCrossRef Bossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR et al (1996) Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem 271:12517–12524PubMedCrossRef
14.
go back to reference Gowen M, Lazner F, Dodds R, Kapadia R, Feild J et al (1999) Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 14:1654–1663PubMedCrossRef Gowen M, Lazner F, Dodds R, Kapadia R, Feild J et al (1999) Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 14:1654–1663PubMedCrossRef
15.
go back to reference Ding KH ZQ, Wyatt B, Rowse J, Shi XM, Xu J, El Refaey M, Hill W, Bollag W, Elsalanty M, Howie N, Insogna K, Chutkan N, Hunter M, Hamrick M, Isales C (2013) Selective amino acid supplementation can exacerbate or prevent low protein-induced bone loss in the aged animal. American Bone and Mineral Society Annual Meeting MO0004. Ding KH ZQ, Wyatt B, Rowse J, Shi XM, Xu J, El Refaey M, Hill W, Bollag W, Elsalanty M, Howie N, Insogna K, Chutkan N, Hunter M, Hamrick M, Isales C (2013) Selective amino acid supplementation can exacerbate or prevent low protein-induced bone loss in the aged animal. American Bone and Mineral Society Annual Meeting MO0004.
16.
go back to reference Tropel P, Noel D, Platet N, Legrand P, Benabid AL et al (2004) Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 295:395–406PubMedCrossRef Tropel P, Noel D, Platet N, Legrand P, Benabid AL et al (2004) Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 295:395–406PubMedCrossRef
17.
go back to reference Shi X, Shi W, Li Q, Song B, Wan M et al (2003) A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep 4:374–380PubMedCentralPubMedCrossRef Shi X, Shi W, Li Q, Song B, Wan M et al (2003) A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep 4:374–380PubMedCentralPubMedCrossRef
18.
go back to reference Hwang SY, Putney JW (2012) Orai1-mediated calcium entry plays a critical role in osteoclast differentiation and function by regulating activation of the transcription factor NFATc1. FASEB J 26:1484–1492PubMedCentralPubMedCrossRef Hwang SY, Putney JW (2012) Orai1-mediated calcium entry plays a critical role in osteoclast differentiation and function by regulating activation of the transcription factor NFATc1. FASEB J 26:1484–1492PubMedCentralPubMedCrossRef
19.
go back to reference Otero JE, Dai S, Foglia D, Alhawagri M, Vacher J et al (2008) Defective osteoclastogenesis by IKKbeta-null precursors is a result of receptor activator of NF-kappaB ligand (RANKL)-induced JNK-dependent apoptosis and impaired differentiation. J Biol Chem 283:24546–24553PubMedCentralPubMedCrossRef Otero JE, Dai S, Foglia D, Alhawagri M, Vacher J et al (2008) Defective osteoclastogenesis by IKKbeta-null precursors is a result of receptor activator of NF-kappaB ligand (RANKL)-induced JNK-dependent apoptosis and impaired differentiation. J Biol Chem 283:24546–24553PubMedCentralPubMedCrossRef
21.
go back to reference Lin RW, Chen CH, Wang YH, Ho ML, Hung SH et al (2009) (-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-kappaB. Biochem Biophys Res Commun 379:1033–1037PubMedCrossRef Lin RW, Chen CH, Wang YH, Ho ML, Hung SH et al (2009) (-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-kappaB. Biochem Biophys Res Commun 379:1033–1037PubMedCrossRef
22.
go back to reference Choi SW, Park KI, Yeon JT, Ryu BJ, Kim KJ et al (2014) Anti-osteoclastogenic activity of matairesinol via suppression of p38/ERK-NFATc1 signaling axis. BMC Complement Altern Med 14:35PubMedCentralPubMedCrossRef Choi SW, Park KI, Yeon JT, Ryu BJ, Kim KJ et al (2014) Anti-osteoclastogenic activity of matairesinol via suppression of p38/ERK-NFATc1 signaling axis. BMC Complement Altern Med 14:35PubMedCentralPubMedCrossRef
23.
go back to reference Revu S, Neregard P, af Klint E, Korotkova M, Catrina AI (2013) Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate. Arthritis Res Ther 15:R205PubMedCentralPubMedCrossRef Revu S, Neregard P, af Klint E, Korotkova M, Catrina AI (2013) Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate. Arthritis Res Ther 15:R205PubMedCentralPubMedCrossRef
24.
go back to reference Soares-Schanoski A, Gomez-Pina V, del Fresno C, Rodriguez-Rojas A, Garcia F et al (2007) 6-Methylprednisolone down-regulates IRAK-M in human and murine osteoclasts and boosts bone-resorbing activity: a putative mechanism for corticoid-induced osteoporosis. J Leukoc Biol 82:700–709PubMedCrossRef Soares-Schanoski A, Gomez-Pina V, del Fresno C, Rodriguez-Rojas A, Garcia F et al (2007) 6-Methylprednisolone down-regulates IRAK-M in human and murine osteoclasts and boosts bone-resorbing activity: a putative mechanism for corticoid-induced osteoporosis. J Leukoc Biol 82:700–709PubMedCrossRef
25.
go back to reference Nair RR, Avila H, Ma X, Wang Z, Lennartz M et al (2008) A novel high-throughput screening system identifies a small molecule repressive for matrix metalloproteinase-9 expression. Mol Pharmacol 73:919–929PubMedCrossRef Nair RR, Avila H, Ma X, Wang Z, Lennartz M et al (2008) A novel high-throughput screening system identifies a small molecule repressive for matrix metalloproteinase-9 expression. Mol Pharmacol 73:919–929PubMedCrossRef
26.
go back to reference Bharti AC, Takada Y, Aggarwal BB (2004) Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 172:5940–5947PubMedCrossRef Bharti AC, Takada Y, Aggarwal BB (2004) Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 172:5940–5947PubMedCrossRef
27.
go back to reference Lecourt S, Mouly E, Freida D, Cras A, Ceccaldi R et al (2013) A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients. PLoS One 8:e69293PubMedCentralPubMedCrossRef Lecourt S, Mouly E, Freida D, Cras A, Ceccaldi R et al (2013) A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients. PLoS One 8:e69293PubMedCentralPubMedCrossRef
28.
go back to reference Mocsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A et al (2004) The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci U S A 101:6158–6163PubMedCentralPubMedCrossRef Mocsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A et al (2004) The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci U S A 101:6158–6163PubMedCentralPubMedCrossRef
29.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408PubMedCrossRef
30.
31.
go back to reference Hampson G, Martin FC, Moffat K, Vaja S, Sankaralingam S et al (2003) Effects of dietary improvement on bone metabolism in elderly underweight women with osteoporosis: a randomised controlled trial. Osteoporos Int 14:750–756PubMedCrossRef Hampson G, Martin FC, Moffat K, Vaja S, Sankaralingam S et al (2003) Effects of dietary improvement on bone metabolism in elderly underweight women with osteoporosis: a randomised controlled trial. Osteoporos Int 14:750–756PubMedCrossRef
32.
go back to reference Reid IR, Cornish J, Baldock PA (2006) Nutrition-related peptides and bone homeostasis. J Bone Miner Res 21:495–500PubMedCrossRef Reid IR, Cornish J, Baldock PA (2006) Nutrition-related peptides and bone homeostasis. J Bone Miner Res 21:495–500PubMedCrossRef
33.
go back to reference Wittrant Y, Gorin Y, Woodruff K, Horn D, Abboud HE et al (2008) High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis. Bone 42:1122–1130PubMedCentralPubMedCrossRef Wittrant Y, Gorin Y, Woodruff K, Horn D, Abboud HE et al (2008) High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis. Bone 42:1122–1130PubMedCentralPubMedCrossRef
34.
go back to reference Hamrick MW, Ding KH, Pennington C, Chao YJ, Wu YD et al (2006) Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin. Bone 39:845–853PubMedCrossRef Hamrick MW, Ding KH, Pennington C, Chao YJ, Wu YD et al (2006) Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin. Bone 39:845–853PubMedCrossRef
35.
go back to reference Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M et al (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3:889–901PubMedCrossRef Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M et al (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3:889–901PubMedCrossRef
36.
go back to reference Matsumoto M, Kogawa M, Wada S, Takayanagi H, Tsujimoto M et al (2004) Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J Biol Chem 279:45969–45979PubMedCrossRef Matsumoto M, Kogawa M, Wada S, Takayanagi H, Tsujimoto M et al (2004) Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J Biol Chem 279:45969–45979PubMedCrossRef
37.
go back to reference Sundaram K, Nishimura R, Senn J, Youssef RF, London SD et al (2007) RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation. Exp Cell Res 313:168–178PubMedCrossRef Sundaram K, Nishimura R, Senn J, Youssef RF, London SD et al (2007) RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation. Exp Cell Res 313:168–178PubMedCrossRef
Metadata
Title
Impact of Dietary Aromatic Amino Acids on Osteoclastic Activity
Authors
Mona El Refaey
Qing Zhong
Ke-Hong Ding
Xing-ming Shi
Jianrui Xu
Wendy B. Bollag
William D. Hill
Norman Chutkan
Richard Robbins
Hugh Nadeau
Maribeth Johnson
Mark W. Hamrick
Carlos M. Isales
Publication date
01-08-2014
Publisher
Springer US
Published in
Calcified Tissue International / Issue 2/2014
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-014-9878-z

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