Skip to main content
Top
Published in: Pediatric Nephrology 4/2010

01-04-2010 | Original Article

Temporal and spatial expression of a growth-regulated network of imprinted genes in growth plate

Authors: Anenisia C. Andrade, Julian C. Lui, Ola Nilsson

Published in: Pediatric Nephrology | Issue 4/2010

Login to get access

Abstract

In mammals, the somatic growth rate is rapid during fetal and early postnatal life and then gradually declines and eventually stops. In search of the fundamental biological mechanism causing coordinated growth deceleration in multiple tissues, a network of imprinted genes was recently identified based on a coordinated decline in expression in several organs during postnatal growth. To explore a possible role in longitudinal bone growth, we characterized expression of the network during postnatal growth in microdissected metaphyseal bone and growth plate zones of 1-, 3-, and 9-week-old rats using real-time PCR. The expression pattern of the network is modified in growth plate. Similar to the coordinated decline previously observed in kidney, lung, liver, and heart, expression of all genes, except Gtl2, decreased with age in metaphyseal bone. On the contrary, Mest, Dlk1, H19, and Gtl2 decreased, and Cdkn1c, Grb10, and Slc38a4 increased with age in growth plate. During differentiation from resting to hypertrophic zone, Mest, Dlk1, Grb10, and Gtl2 expression decreased, whereas Slc38a4 expression increased. In particular, developmental changes in the expression of growth-promoting genes, Mest, Dlk1, Gtl2, and growth-inhibitory genes, Cdkn1c and Grb10, may contribute to the decline in longitudinal bone growth that occurs with age.
Literature
1.
go back to reference Nilsson O, Baron J (2004) Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusion. Trends Endocrinol Metab 15:370–374PubMed Nilsson O, Baron J (2004) Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusion. Trends Endocrinol Metab 15:370–374PubMed
2.
go back to reference Hunziker EB, Schenk RK (1989) Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats. J Physiol 414:55–71PubMed Hunziker EB, Schenk RK (1989) Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats. J Physiol 414:55–71PubMed
3.
go back to reference Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J (2002) The role of the resting zone in growth plate chondrogenesis. Endocrinology 143:1851–1857CrossRefPubMed Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J (2002) The role of the resting zone in growth plate chondrogenesis. Endocrinology 143:1851–1857CrossRefPubMed
4.
go back to reference Schrier L, Ferns SP, Barnes KM, Emons JA, Newman EI, Nilsson O, Baron J (2006) Depletion of resting zone chondrocytes during growth plate senescence. J Endocrinol 189:27–36CrossRefPubMed Schrier L, Ferns SP, Barnes KM, Emons JA, Newman EI, Nilsson O, Baron J (2006) Depletion of resting zone chondrocytes during growth plate senescence. J Endocrinol 189:27–36CrossRefPubMed
5.
go back to reference Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628CrossRefPubMed Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628CrossRefPubMed
6.
go back to reference Kember NF (1979) Proliferation controls in a linear growth system: theoretical studies of cell division in the cartilage growth plate. J Theor Biol 78:365–374CrossRefPubMed Kember NF (1979) Proliferation controls in a linear growth system: theoretical studies of cell division in the cartilage growth plate. J Theor Biol 78:365–374CrossRefPubMed
7.
go back to reference Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S, Aknin C, Severac D, Chotard L, Kahli M, Le Digarcher A, Pavlidis P, Journot L (2006) Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev Cell 11:711–722CrossRefPubMed Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S, Aknin C, Severac D, Chotard L, Kahli M, Le Digarcher A, Pavlidis P, Journot L (2006) Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev Cell 11:711–722CrossRefPubMed
8.
go back to reference Lui JC, Finkielstain GP, Barnes KM, Baron J (2008) An imprinted gene network that controls mammalian somatic growth is down-regulated during postnatal growth deceleration in multiple organs. Am J Physiol Regul Integr Comp Physiol 295:R189–R196PubMed Lui JC, Finkielstain GP, Barnes KM, Baron J (2008) An imprinted gene network that controls mammalian somatic growth is down-regulated during postnatal growth deceleration in multiple organs. Am J Physiol Regul Integr Comp Physiol 295:R189–R196PubMed
9.
go back to reference Nilsson O, Parker EA, Hegde A, Chau M, Barnes KM, Baron J (2007) Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol 193:75–84CrossRefPubMed Nilsson O, Parker EA, Hegde A, Chau M, Barnes KM, Baron J (2007) Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol 193:75–84CrossRefPubMed
10.
go back to reference Heinrichs C, Yanovski JA, Roth AH, Yu YM, Domené HM, Yano K, Cutler GB Jr, Baron J (1994) Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate. Endocrinology 135:1113–1118CrossRefPubMed Heinrichs C, Yanovski JA, Roth AH, Yu YM, Domené HM, Yano K, Cutler GB Jr, Baron J (1994) Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate. Endocrinology 135:1113–1118CrossRefPubMed
11.
go back to reference Goidin D, Mamessier A, Staquet MJ, Schmitt D, Berthier-Vergnes O (2001) Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes as internal standard for quantitative comparison of mRNA levels in invasive and noninvasive human melanoma cell subpopulations. Anal Biochem 295:17–21CrossRefPubMed Goidin D, Mamessier A, Staquet MJ, Schmitt D, Berthier-Vergnes O (2001) Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes as internal standard for quantitative comparison of mRNA levels in invasive and noninvasive human melanoma cell subpopulations. Anal Biochem 295:17–21CrossRefPubMed
12.
go back to reference Tsuji N, Kamagata C, Furuya M, Kobayashi D, Yagihashi A, Morita T, Horita S, Watanabe N (2002) Selection of an internal control gene for quantitation of mRNA in colonic tissues. Anticancer Res 22:4173–4178PubMed Tsuji N, Kamagata C, Furuya M, Kobayashi D, Yagihashi A, Morita T, Horita S, Watanabe N (2002) Selection of an internal control gene for quantitation of mRNA in colonic tissues. Anticancer Res 22:4173–4178PubMed
13.
go back to reference Parker EA, Hegde A, Buckley M, Barnes KM, Baron J, Nilsson O (2007) Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. J Endocrinol 194:31–40CrossRefPubMed Parker EA, Hegde A, Buckley M, Barnes KM, Baron J, Nilsson O (2007) Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. J Endocrinol 194:31–40CrossRefPubMed
14.
go back to reference Smith FM, Garfield AS, Ward A (2006) Regulation of growth and metabolism by imprinted genes. Cytogenet Genome Res 113:279–291CrossRefPubMed Smith FM, Garfield AS, Ward A (2006) Regulation of growth and metabolism by imprinted genes. Cytogenet Genome Res 113:279–291CrossRefPubMed
15.
go back to reference Charalambous M, Smith FM, Bennett WR, Crew TE, Mackenzie F, Ward A (2003) Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proc Natl Acad Sci USA 100:8292–8297CrossRefPubMed Charalambous M, Smith FM, Bennett WR, Crew TE, Mackenzie F, Ward A (2003) Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proc Natl Acad Sci USA 100:8292–8297CrossRefPubMed
16.
go back to reference Shiura H, Miyoshi N, Konishi A, Wakisaka-Saito N, Suzuki R, Muguruma K, Kohda T, Wakana S, Yokoyama M, Ishino F, Kaneko-Ishino T (2005) Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Biochem Biophys Res Commun 329:909–916CrossRefPubMed Shiura H, Miyoshi N, Konishi A, Wakisaka-Saito N, Suzuki R, Muguruma K, Kohda T, Wakana S, Yokoyama M, Ishino F, Kaneko-Ishino T (2005) Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Biochem Biophys Res Commun 329:909–916CrossRefPubMed
17.
go back to reference Lee MH, Reynisdottir I, Massague J (1995) Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev 9:639–649CrossRefPubMed Lee MH, Reynisdottir I, Massague J (1995) Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev 9:639–649CrossRefPubMed
18.
go back to reference Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (1995) p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 9:650–662CrossRefPubMed Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (1995) p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 9:650–662CrossRefPubMed
19.
go back to reference Hatada I, Mukai T (1995) Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. Nat Genet 11:204–206CrossRefPubMed Hatada I, Mukai T (1995) Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. Nat Genet 11:204–206CrossRefPubMed
20.
go back to reference Taniura H, Taniguchi N, Hara M, Yoshikawa K (1998) Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J Biol Chem 273:720–728CrossRefPubMed Taniura H, Taniguchi N, Hara M, Yoshikawa K (1998) Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J Biol Chem 273:720–728CrossRefPubMed
21.
go back to reference Gérard M, Hernandez L, Wevrick R, Stewart CL (1999) Disruption of the mouse necdin gene results in early post-natal lethality. Nat Genet 23:199–202CrossRefPubMed Gérard M, Hernandez L, Wevrick R, Stewart CL (1999) Disruption of the mouse necdin gene results in early post-natal lethality. Nat Genet 23:199–202CrossRefPubMed
22.
go back to reference Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H (2000) Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 9:3101–3110CrossRefPubMed Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H (2000) Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 9:3101–3110CrossRefPubMed
23.
go back to reference Lazarus JE, Hegde A, Andrade AC, Nilsson O, Baron J (2007) Fibroblast growth factor expression in the postnatal growth plate. Bone 40:577–586CrossRefPubMed Lazarus JE, Hegde A, Andrade AC, Nilsson O, Baron J (2007) Fibroblast growth factor expression in the postnatal growth plate. Bone 40:577–586CrossRefPubMed
24.
go back to reference Finkielstain GP, Forcinito P, Lui JC, Barnes KM, Marino R, Makaroun S, Nguyen V, Lazarus JE, Nilsson O, Baron J (2009) An extensive genetic program occurring during postnatal growth in multiple tissues. Endocrinology 150:1791–1800CrossRefPubMed Finkielstain GP, Forcinito P, Lui JC, Barnes KM, Marino R, Makaroun S, Nguyen V, Lazarus JE, Nilsson O, Baron J (2009) An extensive genetic program occurring during postnatal growth in multiple tissues. Endocrinology 150:1791–1800CrossRefPubMed
25.
go back to reference Marino R, Hegde A, Barnes KM, Schrier L, Emons JA, Nilsson O, Baron J (2008) Catch-up growth after hypothyroidism is caused by delayed growth plate senescence. Endocrinology 149:1820–1828CrossRefPubMed Marino R, Hegde A, Barnes KM, Schrier L, Emons JA, Nilsson O, Baron J (2008) Catch-up growth after hypothyroidism is caused by delayed growth plate senescence. Endocrinology 149:1820–1828CrossRefPubMed
26.
go back to reference Poirier F, Chan CT, Timmons PM, Robertson EJ, Evans MJ, Rigby PW (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 113:1105–1114PubMed Poirier F, Chan CT, Timmons PM, Robertson EJ, Evans MJ, Rigby PW (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 113:1105–1114PubMed
27.
go back to reference Leighton PA, Ingram RS, Eggenschwiler J, Efstratiadis A, Tilghman SM (1995) Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375:34–39CrossRefPubMed Leighton PA, Ingram RS, Eggenschwiler J, Efstratiadis A, Tilghman SM (1995) Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375:34–39CrossRefPubMed
28.
go back to reference Gabory A, Ripoche MA, Yoshimizu T, Dandolo L (2006) The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res 113:188–193CrossRefPubMed Gabory A, Ripoche MA, Yoshimizu T, Dandolo L (2006) The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res 113:188–193CrossRefPubMed
Metadata
Title
Temporal and spatial expression of a growth-regulated network of imprinted genes in growth plate
Authors
Anenisia C. Andrade
Julian C. Lui
Ola Nilsson
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 4/2010
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-009-1339-y

Other articles of this Issue 4/2010

Pediatric Nephrology 4/2010 Go to the issue