Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Pediatric Nephrology
Erschienen in: Pediatric Nephrology 4/2013

01.04.2013 | Review

Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling

verfasst von: Colin Farquharson, S. Faisal Ahmed

Erschienen in: Pediatric Nephrology | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.
Literatur
1.
Nilsson O, Marino R, De Luca F, Phillip M, Baron J (2005) Endocrine regulation of the growth plate. Horm Res 64:157–165PubMedCrossRef
2.
Waters MJ, Hoang HN, Fairlie DP, Pelekanos RA, Brown RJ (2006) New insights into growth hormone action. J Mol Endocrinol 36:1–7PubMedCrossRef
3.
MacRae VE, Farquharson C, Ahmed SF (2006) The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology 45:11–19PubMedCrossRef
4.
MacRae VE, Wong SC, Farquharson C, Ahmed SF (2006) Cytokine actions in growth disorders associated with pediatric chronic inflammatory diseases. Int J Mol Med 18:1011–1018PubMed
5.
Martensson K, Chrysis D, Savendahl L (2004) Interleukin-1 beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones. J Bone Miner Res 19:1805–1812PubMedCrossRef
6.
MacRae VE, Farquharson C, Ahmed SF (2006) The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines. J Endocrinol 189:319–328PubMedCrossRef
7.
Pass C, MacRae VE, Huesa C, Ahmed SF, Farquharson C (2012) SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis. J Bone Miner Res 27:1055–1066PubMedCrossRef
8.
Tan JC, Rabkin R (2005) Suppressors of cytokine signaling in health and disease. Pediatr Nephrol 20:567–575PubMedCrossRef
9.
10.
Mackie EJ, Tatarczuch L, Mirams M (2011) The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification. J Endocrinol 211:109–121PubMedCrossRef
11.
Hunziker EB, Schenk RK, Cruzorive LM (1987) Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone-growth. J Bone Joint Surg Am 69:162–173PubMed
12.
Buckwalter JA, Mower D, Ungar R, Schaeffer J, Ginsberg B (1986) Morphometric analysis of chondrocyte hypertrophy. J Bone Joint Surg Am 68:243–255PubMed
13.
Farnum CE, Wilsman NJ (1987) Morphological stages of the terminal hypertrophic chondrocyte of growth plate cartilage. Anat Rec 219:221–232PubMedCrossRef
14.
Loqman MY, Bush PG, Farquharson C, Hall AC (2010) A cell shrinkage artefact in growth plate chondrocytes with common fixative solutions: importance of fixative osmolarity for maintaining morphology. Eur Cell Mater 19:214–227PubMed
15.
Schmid TM, Linsenmayer TF (1985) Immunohistochemical localization of short chain cartilage collagen (type-x) in avian-tissues. J Cell Biol 100:598–605PubMedCrossRef
16.
Farquharson C, Whitehead CC, Loveridge N (1994) Alterations in glycosaminoglycan concentration and sulfation during chondrocyte maturation. Calcif Tissue Int 54:296–303PubMedCrossRef
17.
Ciancaglini P, Yadav MC, Simao AMS, Narisawa S, Pizauro JM, Farquharson C, Hoylaerts MF, Millan JL (2010) Kinetic analysis of substrate utilization by native and TNAP-, NPP1-, or PHOSPHO1-deficient matrix vesicles. J Bone Miner Res 25:716–723PubMed
18.
Roberts SJ, Stewart AJ, Sadler PJ, Farquharson C (2004) Human PHOSPH01 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities. Biochem J 382:59–65PubMedCrossRef
19.
Isaksson OGP, Jansson JO, Gause IAM (1982) Growth-hormone stimulates longitudinal bone-growth directly. Science 216:1237–1239PubMedCrossRef
20.
Nilsson A, Isgaard J, Lindahl A, Dahlstrom A, Skottner A, Isaksson OGP (1986) Regulation by growth-hormone of number of chondrocytes containing IGF-1 in rat growth plate. Science 233:571–574PubMedCrossRef
21.
Pecoits R, Sylvestre LC, Stenvinkel P (2005) Chronic kidney disease and inflammation in pediatric patients: from bench to playground. Pediatr Nephrol 20:714–720CrossRef
22.
Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimburger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia—the good, the bad, and the ugly. Kidney Int 67:1216–1233PubMedCrossRef
23.
Goldenberg N, Barkan A (2007) Factors regulating growth hormone secretion in humans. Endocrinol Metab Clin North Am 36:37–43PubMedCrossRef
24.
Salmon WD, Daughaday WH (1957) A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 49:825–836PubMed
25.
Mathews LS, Hammer RE, Behringer RR, Dercole AJ, Bell GI, Brinster RL, Palmiter RD (1988) Growth enhancement of transgenic mice expressing human insulin-like growth factor-i. Endocrinology 123:2827–2833PubMedCrossRef
26.
Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A (2001) Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 229:141–162PubMedCrossRef
27.
Ahmed SF, Farquharson C (2010) The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins. J Endocrinol 206:249–259PubMedCrossRef
28.
Yakar S, Courtland HW, Clemmons D (2010) IGF-1 and bone: new discoveries from mouse models. J Bone Miner Res 25:2267–2276CrossRef
29.
Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, LeRoith D (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 96:7324–7329PubMedCrossRef
30.
Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson OGP, Jansson JO, Ohlsson C (1999) Liver-derived insulin-like growth factor I (IGF-1) is the principal source of IGF-1 in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 96:7088–7092PubMedCrossRef
31.
Cui Y, Hosui A, Sun R, Shen K, Gavrilova O, Chen W, Cam MC, Gao B, Robinson GW, Hennighausen L (2007) Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration. Hepatology 46:504–513PubMedCrossRef
32.
Yakar S, Rosen CJ, Bouxsein ML, Sun H, Mejia W, Kawashima Y, Wu YJ, Emerton K, Williams V, Jepsen K, Schaffler MB, Majeska RJ, Gavrilova O, Gutierrez M, Hwang D, Pennisi P, Frystyk J, Boisclair Y, Pintar J, Jasper H, Domene H, Cohen P, Clemmons D, LeRoith D (2009) Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. FASEB J 23:709–719PubMedCrossRef
33.
Govoni KE, Lee SK, Chung Y-S, Behringer RR, Wergedal JE, Baylink DJ, Mohan S (2007) Disruption of insulin-like growth factor-I expression in type II alpha I collagen-expressing cells reduces bone length and width in mice. Physiol Genomics 30:354–362PubMedCrossRef
34.
Wang Y, Cheng Z, ElAlieh HZ, Nakamura E, Nguyen M-T, Mackem S, Clemens TL, Bikle DD, Chang W (2011) IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway. J Bone Miner Res 26:1437–1446PubMedCrossRef
35.
Kuizon BD, Salusky IB (1999) Growth retardation in children with chronic renal failure. J Bone Miner Res 14:1680–1690PubMedCrossRef
36.
Mahan JD (2006) Applying the growth failure in CKD consensus conference: evaluation and treatment algorithm in children with chronic kidney disease. Growth Horm IGF Res 16:S68–S78PubMedCrossRef
37.
Rabkin R, Sun DF, Chen Y, Tan J, Schaefer F (2005) Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. Pediatr Nephrol 20:313–318PubMedCrossRef
38.
Schaefer F, Chen Y, Tsao T, Nouri P, Rabkin R (2001) Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. J Clin Invest 108:467–475PubMed
39.
Cheung WW, Paik KH, Mak RH (2010) Inflammation and cachexia in chronic kidney disease. Pediatr Nephrol 25:711–724PubMedCrossRef
40.
Barreto DV, Barreto FC, Liabeuf S, Temmar M, Lemke H-D, Tribouilloy C, Choukroun G, Vanholder R, Massy ZA, European Uremic Toxin Work G (2010) Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney Int 77:550–556PubMedCrossRef
41.
Herbelin A, Urena P, Nguyen AT, Zingraff J, Descampslatscha B (1991) Elevated circulating levels of interleukin-6 in patients with chronic-renal-failure. Kidney Int 39:954–960PubMedCrossRef
42.
Cheung WW, Kuo H-J, Markison S, Chen C, Foster AC, Marks DL, Mak RH (2007) Peripheral administration of the melanocortin-4 receptor antagonist NBI-12i ameliorates uremia-associated cachexia in mice. J Am Soc Nephrol 18:2517–2524PubMedCrossRef
43.
Zoccali C, Tripepi G, Mallamaci F (2006) Dissecting inflammation in ESRD: do cytokines and C-reactive protein have a complementary prognostic value for mortality in dialysis patients? J Am Soc Nephrol 17:S169–S173PubMedCrossRef
44.
Raj DSC, Dominic EA, Pai A, Osman F, Morgan M, Pickett G, Shah VO, Ferrando A, Moseley P (2005) Skeletal muscle, cytokines, and oxidative stress in end-stage renal disease. Kidney Int 68:2338–2344PubMedCrossRef
45.
Garibotto G, Sofia A, Procopio V, Villaggio B, Tarroni A, Di Martino M, Cappelli V, Gandolfo MT, Aloisi F, De Cian F, Sala MR, Verzola D (2006) Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state. Kidney Int 70:384–390PubMedCrossRef
46.
Ihle JN, Kerr IM (1995) Jaks and stats in signaling by the cytokine receptor superfamily. Trends Genet 11:69–74PubMedCrossRef
47.
Leaman DW, Leung S, Li XX, Stark GR (1996) Regulation of STAT-dependent pathways by growth factors and cytokines. FASEB J 10:1578–1588PubMed
48.
O’Sullivan LA, Liongue C, Lewis RS, Stephenson SEM, Ward AC (2007) Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol 44:2497–2506PubMedCrossRef
49.
Berry JL, Farquharson C, Whitehead CC, Mawer EB (1996) Growth plate chondrocyte vitamin D receptor number and affinity are reduced in avian tibial dyschondroplastic lesions. Bone 19:197–203PubMedCrossRef
50.
Gevers EF, Hannah MJ, Waters MJ, Robinson ICAF (2009) Regulation of rapid signal transducer and activator of transcription-5 phosphorylation in the resting cells of the growth plate and in the liver by growth hormone and feeding. Endocrinology 150:3627–3636PubMedCrossRef
51.
Pass C, MacRae VE, Ahmed SF, Farquharson C (2009) Inflammatory cytokines and the GH/IGF-1 axis: novel actions on bone growth. Cell Biochem Funct 27:119–127PubMedCrossRef
52.
Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 94:3801–3804PubMedCrossRef
53.
Meraz MA, White JM, Sheehan KCF, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, CarverMoore K, DuBois RN, Clark R, Aguet M, Schreiber RD (1996) Targeted disruption of the STAT1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84:431–442PubMedCrossRef
54.
Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG (2003) Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 349:1139–1147PubMedCrossRef
55.
Adams TE, Hansen JA, Starr R, Nicola NA, Hilton DJ, Billestrup N (1998) Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling. J Biol Chem 273:1285–1287PubMedCrossRef
56.
Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, Hilton DJ, Alexander WS (2001) Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc Natl Acad Sci USA 98:9324–9329PubMedCrossRef
57.
Rastmanesh MM, Bluyssen HAR, Joles JA, Boer P, Willekes N, Braam B (2008) Increased expression of SOCS3 in monocytes and SOCS1 in lymphocytes correlates with progressive loss of renal function and cardiovascular risk factors in chronic kidney disease. Eur J Pharmacol 593:99–104PubMedCrossRef
58.
Rastmanesh MM, Braam B, Joles JA, Boer P, Bluyssen HAR (2009) Increased SOCS expression in peripheral blood mononuclear cells of end-stage renal disease patients is related to inflammation and dialysis modality. Eur J Pharmacol 602:163–167PubMedCrossRef
59.
Macrae VE, Horvat S, Pells SC, Dale H, Collinson RS, Pitsillides AA, Ahmed SF, Farquharson C (2009) Increased bone mass, altered trabecular architecture and modified growth plate organization in the growing skeleton of SOCS2 deficient mice. J Cell Physiol 218:276–284PubMedCrossRef
60.
Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C (2005) Reduced bone mineral density in SOCS-2-deficient mice. Pediatr Res 57:223–226PubMedCrossRef
61.
Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS (2000) Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 405:1069–1073PubMedCrossRef
62.
Horvat S, Medrano JF (2001) Lack of Socs2 expression causes the high-growth phenotype in mice. Genomics 72:209–212PubMedCrossRef
63.
Medrano JF, Pomp D, Sharrow L, Bradford GE, Downs TR, Frohman LA (1991) Growth-hormone and insulin-like growth factor-i measurements in high growth (hg) mice. Genet Res 58:67–74PubMedCrossRef
64.
Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, Davey HW, Nicola NA, Hilton DJ, Alexander WS (2002) Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b). Mol Endocrinol 16:1394–1406PubMedCrossRef
65.
Greenhalgh CJ, Rico-Bautista E, Lorentzon M, Thaus AL, Morgan PO, Willson TA, Zervoudakis P, Metcalf D, Street I, Nicola NA, Nash AD, Fabri LJ, Norstedt G, Ohlsson C, Flores-Morales A, Alexander WS, Hilton DJ (2005) SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest 115:397–406PubMed
66.
Abe T, Nomura S, Nakagawa R, Fujimoto M, Kawase I, Naka T (2006) Osteoblast differentiation is impaired in SOCS-1-deficient mice. J Bone Miner Metab 24:283–290PubMedCrossRef
67.
Dey BR, Spence SL, Nissley P, Furlanetto RW (1998) Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. J Biol Chem 273:24095–24101PubMedCrossRef
68.
Michaylira CZ, Simmons JG, Ramocki NM, Scull BP, McNaughton KK, Fuller CR, Lund PK (2006) Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-1 in vivo. Am J Physiol Gastrointest Liver Physiol 291:G472–G481PubMedCrossRef
69.
Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JRB, Stevens S, Hall AS, Samani NJ, Shields B, Prokopenko I, Farrall M, Dominiczak A, Johnson T, Bergmann S, Beckmann JS, Vollenweider P, Waterworth DM, Mooser V, Palmer CNA, Morris AD, Ouwehand WH, Caulfield M, Munroe PB, Hattersley AT, McCarthy MI, Frayling TM, Diabet Genetics I, Wellcome Trust Case Control C, Cambridge GEMC (2008) Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genet 40:575–583PubMedCrossRef
70.
Suda K, Iguchi G, Yamamoto M, Handayaningsih AE, Nishizawa H, Takahashi M, Okimura Y, Kaji H, Chihara K, Takahashi Y (2011) A case of gigantism associated with a missense mutation in the SOCS2 gene. Endocr Rev 32:OR36-1
71.
Cheung WW, Rosengren S, Boyle DL, Mak RH (2008) Modulation of melanocortin signaling ameliorates uremic cachexia. Kidney Int 74:180–186PubMedCrossRef
72.
Sun D, Zheng L, Tummala P, Oh J, Schaefer F, Rabkin R (2004) GH-mediated JAK/STAT signaling is impaired in skeletal muscle in chronic uremia. Growth Horm IGF Res 14:131–132
73.
Mehls O, Lindberg A, Nissel R, Haffner D, Hokken-Koelega A, Ranke MB (2010) Predicting the response to growth hormone treatment in short children with chronic kidney disease. J Clin Endocrinol Metab 95:686–692PubMedCrossRef
74.
Bullock AN, Debreczeni JE, Edwards AM, Sundstrom M, Knapp S (2006) Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Proc Natl Acad Sci USA 103:7637–7642PubMedCrossRef
Metadaten
Titel
Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling
verfasst von
Colin Farquharson
S. Faisal Ahmed
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 4/2013
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2271-0

Weitere Artikel der Ausgabe 4/2013

Pediatric Nephrology 4/2013 Zur Ausgabe

Review

Searching the optimal PTH target range in children undergoing peritoneal dialysis: New insights from international cohort studies

Original Article

Aldosterone contributes to elevated left ventricular mass in black boys

Review

Phosphate binders, vitamin D and calcimimetics in the management of chronic kidney disease–mineral bone disorders (CKD-MBD) in children

Review

Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in innate immunity?

Clinical Quiz

Ocular involvement in a child with medullary nephrocalcinosis: Questions

Brief Report

Performing renal biopsies in children under general anaesthesia in the lateral position

Neu im Fachgebiet Pädiatrie

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise