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01-04-2010 | Review

Growth-plate cartilage in chronic renal failure

Author: Cheryl P. Sanchez

Published in: Pediatric Nephrology | Issue 4/2010

Abstract

Bone growth occurs in the growth-plate cartilage located at the ends of long bones. Changes in the architecture, abnormalities in matrix organization, reduction in protein staining and RNA expression of factors involved in cell signaling have been described in the growth-plate cartilage of nephrectomized animals. These changes can lead to a smaller growth plate associated with decrease in chondrocyte proliferation, delayed hypertrophy, and prolonged initiation of mineralization and vascular invasion. As a result, chronic renal failure can result in stunted body growth and skeletal deformities. Multiple etiologic factors can contribute to impaired bone growth in renal failure, including suboptimal nutrition, metabolic acidosis, and secondary hyperparathyroidism. Recent findings have also shown the tight connection between chondro/osteogenesis, hematopoiesis, and immunogenesis.

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

Vortkamp A, Lee K, Lankse B, Segre GV, Kronenberg HM, Tabin CJ (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613–622CrossRefPubMed

Kronenberg HM (2006) PTHrP and skeletal development. Ann NY Acad Sci 1068:1–13CrossRefPubMed

Alvarez J, Sohn P, Zeng X, Doetschman T, Robbins D, Serra R (2002) TGFβ2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129:1913–1924PubMed

MacLean HE, Guo J, Knight MC, Zhang P, Cobrinik D, Kronenberg HM (2004) The cyclin-dependent kinase inhibitor p57^Kip2 mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest 113:1334–1343PubMed

Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VLJ, Kronenberg HM, Mulligan RC (1994) Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 8:277–289CrossRefPubMed

Amizuka N, Warshawsky H, Henderson JE, Goltzman D, Karaplis AC (1994) Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. J Cell Biol 126:1611–1623CrossRefPubMed

Weir EC, Philbrick WM, Amling M, Neff LA, Baron R, Broadus AE (1996) Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proc Natl Acad Sci USA 93:10240–10245CrossRefPubMed

Zhang M, Xie R, Hou W, Wang B, Shen R, Wang X, Wang Q, Zhu T, Jonason J, Chen D (2009) PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin-D₁-dependent Runx2 and Runx3 phosphorylation, ubiquitylation and proteasomal degradation. J Cell Sci 122:1382–1389CrossRefPubMed

10.

Dong Y, Soung YD, Schwarz E, O'Keefe R, Drissi H (2006) Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol 208:77–86CrossRefPubMed

11.

Yoshida C, Komori T (2005) Role of Runx proteins in chondrogenesis. Crit Rev Eukaryot Gene Expr 15:243–254PubMed

12.

Komori T (2005) Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem 95:445–453CrossRefPubMed

13.

Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T (2004) Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol 166:85–95CrossRefPubMed

14.

Enomoto H, Shiojiri S, Hoshi K, Furuichi T, Fukuyama R, Yoshida C, Kanatani N, Nakamura R, Mizuno A, Zanno A, Yano K, Yasuda H, Higashio K, Takada K, Komori T (2003) Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. J Biol Chem 278:23971–23977CrossRefPubMed

15.

Hunziker EB, Kapfinger E, Saager C (1999) Hypertrophy of growth plate chondrocytes in vivo is accompanied by modulations in the activity state and surface area of their cytoplasmic organelles. Histochem Cell Biol 112:115–123CrossRefPubMed

16.

Reinecke M, Schmid AC, Heyberger-Meyer B, Hunziker EB, Zapf J (2000) Effect of growth hormone and insulin-like growth factor I (IGF-I) on the expression of IGF-I messenger ribonucleic acid and peptide in rat tibial growth plate and articular chondrocytes in vivo. Endocrinology 141:2847–2853CrossRefPubMed

17.

Srinivas V, Bohensky J, Shapiro IM (2009) Autophagy: a new phase in the maturation of growth plate chondrocytes is regulated by HIF, mTOR and AMP kinase. Cells Tissues Organs 189:88–92CrossRefPubMed

18.

Li J, Sarosi I, Yan X-Q, Morony S, Capparelli C, Tan H-L, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan S-C, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ (2000) RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA 97:1566–1571CrossRefPubMed

19.

Zelzer E, Mamluk R, Ferrara N, Johnson R, Schipani E, Olsen B (2006) VEGFA is necessary for chondrocyte survival during bone development. Development 131:2161–2171CrossRef

20.

Stricker S, Fundele R, Vortkamp A, Mundlos S (2002) Role of Runx genes in chondrocyte differentiation. Dev Biol 245:95–108CrossRefPubMed

21.

Hofbauer L, Heufelder A (2001) Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243–253CrossRefPubMed

22.

Walsh M, Kim N, Kadono Y, Rho J, Lee S, Lorenzo J, Choi Y (2006) Osteoimmunology: interplay between the immune system and bone metabolism. Ann Rev Immunol 24:33–63CrossRef

23.

Sharma AP, Sharma RK, Kapoor R, Kornecki A, Sural S, Filler G (2007) Incomplete distal renal tubular acidosis affects growth in children. Nephrol Dial Transplant 22:2879–2885CrossRefPubMed

24.

Challa A, Krieg RJ, Thabet MA, Veldhuis JD, Chan JC (1993) Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol 265:E547–E553PubMed

25.

Goldberg R, Reshef-Bankai E, Coleman R, Green J, Maor G (2006) Chronic acidosis-induced growth retardation is mediated by proton-induced expression of Gs protein. J Bone Miner Res 215:703–713CrossRef

26.

Green J, Maor G (2000) Effect of metabolic acidosis on the growth hormone/IGF-I endocrine axis in skeletal growth centers. Kidney Int 57:2258–2267CrossRefPubMed

27.

Waldman S, Couto D, Omelon S, Kandel R (2004) Effect of sodium bicarbonate on extracellular pH, matrix accumulation, and morphology of cultured articular chondrocytes. Tissue Eng 10:1633–1640CrossRefPubMed

28.

Wu M, Urban J, Cui Z, Xu X (2007) Effect of extracellular ph on matrix synthesis by chondrocytes in 3D agarose gel. Biotechnol Prog 23:430–434CrossRefPubMed

29.

Jandziszak K, Suarez C, Saenger PH, Brion LP (2000) Time course of the response to recombinant growth hormone in acidotic mice. Pediatr Nephrol 14:922–926CrossRefPubMed

30.

Gat-Yablonski G, Shtaif B, Abraham E, Phillip M (2008) Nutrition-induced catch-up growth at the growth plate. J Pediatr Endocrinol Metab 21:879–893PubMed

31.

Farnum CA, Lee AO, O'Hara K, Wilsman NJ (2003) Effect of short-term fasting on bone elongation rates: an analysis of catch-up growth in young male rats. Pediatr Res 53:33–41PubMed

32.

Molinos I, Santos F, Carbajo-Perez E, Garcia E, Rodriguez J, Garcia-Alvarez O, Gil H, Ordonez FA, Loredo V, Mallada L (2006) Catch-up growth follows an abnormal pattern in experimental renal insufficiency and growth hormone treatment normalizes it. Kidney Int 70:1955–1961PubMed

33.

Gevers E, Hannah M, Waters M, Robinson I (2009) Regulation of rapid stat5 phosphorylation in the resting cells of the growth plate and in the liver by growth hormone and feeding. Endocrinology 150:3627–3636CrossRef

34.

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

35.

Ram PA, Waxman DJ (1999) SOCS/CIS protein inhibition of growth hormone-stimulated STAT₅ signaling by multiple mechanisms. J Biol Chem 274:35553–35561CrossRefPubMed

36.

Tollet-Egnell P, Flores-Morales A, Stavreus-Evers A, Sahlin L, Norstedt G (1999) Growth hormone regulation of SOCS-2, SOCS-3, and CIS messenger ribonucleic acid expression in the rat. Endocrinology 140:3693–3704CrossRefPubMed

37.

Gat-Yablonski G, Ben-Ari T, Shtaif B, Potievsky O, Moran O, Eshet R, Maor G, Segev Y, Phillip M (2004) Leptin reverses the inhibitory effect of caloric restriction on longitudinal growth. Endocrinology 145:343–350CrossRefPubMed

38.

Arbeiter A, Buscher R, Petersenn S, Hauffa B, Mann K, Hoyer PF (2009) Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation. Nephrol Dial Transplant 24:643–646CrossRefPubMed

39.

Cobo A, Lopez JM, Carbajo E, Santos F, Alvarez J, Fernandez M, Weruaga A (1999) Growth plate cartilage formation and resorption are differentially expressed in growth retarded uremic rats. J Am Soc Nephrol 10:971–979PubMed

40.

Sanchez C, He Y, Leiferman E, Wilsman N (2004) Bone elongation in rats with renal failure and mild or advanced secondary hyperparathyroidism. Kidney Int 65:1740–1748CrossRefPubMed

41.

Sanchez C, He Y (2007) Bone growth during daily or intermittent calcitriol treatment during renal failure with advanced secondary hyperparathyroidism. Kidney Int 72:582–591CrossRefPubMed

42.

Alvarez J, Balbin M, Fernandez M, Lopez JM (2001) Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure. J Bone Miner Res 16:511–524CrossRefPubMed

43.

Bengtsson T, Aszodi A, Nicolae C, Hunziker EB, Lundgren-Akerlund E, Fassler R (2005) Loss of α₁₀β₁ integrin expression leads to moderate dysfunction of growth plate chondrocytes. J Cell Sci 118:929–936CrossRefPubMed

44.

Hopper T, Wehrli FW, Saha P, Andre J, Wright A, Sanchez C, Leonard M (2007) Quantitative microcomputed tomography assessment of intratrabecular, intertrabecular, and cortical bone architecture in a rat model of severe renal osteodystrophy. J Comput Assist Tomogr 31:320–328CrossRefPubMed

45.

Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R (2003) Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas. Eur J Endocrinol 148:403–411CrossRefPubMed

46.

Masuyama R, Stockmans I, Torrekens S, Looveren RV, Maes C, Carmeliet P, Bouillon R, Carmeliet G (2006) Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J Clin Invest 116:3150–3159CrossRefPubMed

47.

Chang W, Tu C, Chen T, Bikle D, Shoback D (2008) The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development. Sci Signal 1:ra1CrossRefPubMed

48.

Canadillas S, Canalejo A, Santamaria R, Rodriguez ME, Estepa JC, Martin-Malo A, Bravo J, Ramos B, Aguilera-Tejero E, Rodriguez M, Almaden Y (2005) Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans. J Am Soc Nephrol 16:2190–2197CrossRefPubMed

49.

Nakagawa K, Perez E, Oh J, Santos F, Geldyyev A, Gross M, Schaefer F, Schmitt C (2008) Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia. Nephrol Dial Transplant 23:2761–2767CrossRefPubMed

50.

Muscheites J, Wigger M, Drueckler E, Fischer D, Kundt G, Haffner D (2008) Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol 23:1823–1829CrossRefPubMed

51.

Silverstein D, Kher K, Moudgil A, Khurana M, Wilcox J, Moylan K (2008) Cinacalcet is efficacious in pediatric dialysis patients. Pediatr Nephrol 23:1817–1822CrossRefPubMed

52.

Kolek O, Hines E, Jones M, LeSueur L, Lipko M, Kiela P, Collins J, Haussler M, Ghishan F (2005) 1α, 25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289:G1036–G1042CrossRefPubMed

53.

Strom T, Jüppner H (2008) PHEX, FGF23, DMP1 and beyond. Curr Opin Nephrol Hypertens 17:357–362CrossRefPubMed

54.

Julien M, Khoshniat S, Lacreusette A, Gatius M, Bozec A, Wagner E, Wittrant Y, Masson M, Weiss P, Beck L, Magne D, Guicheux J (2009) Phosphate-dependent regulation of MGP in osteoblasts: Role of ERK1/2 and Fra-1. J Bone Miner Res. doi:10.1359/jbmr.090508 PubMed

55.

Wesseling-Perry K, Pereira R, Wang H, Elashoff RM, Sahney S, Gales B, Jüppner H, Salusky IB (2009) Relationship between plasma FGF-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. J Clin Endocrinol Metab 94:511–517CrossRefPubMed

56.

Mensah K, Li J, Schwarz E (2009) The emerging field of osteoimmunology. Immunol Res. doi:10.1007/s12026-009-8093-x PubMed

57.

Nakashima T, Takayanagi H (2009) Osteoclasts and the immune system. J Bone Miner Metab. doi:10.1007/s00774-009-0089-z PubMed

58.

Neves P, Trivino J, Casaubon F, Santos V, Mendes P, Romao P, Bexiga I, Bernardo I (2006) Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol. Int Urol Nephrol 38:175–177CrossRefPubMed

59.

Lin C, Hung C, Yang C, Huang C (2004) Improved anemia and reduced erythropoietin need by medical or surgical intervention of secondary hyperparathyroidism in hemodialysis patients. Ren Fail 26:289–295CrossRefPubMed

60.

Sweeney E, Campbell M, Watkins K, Hunter C, Jacenko O (2008) Altered endochondral ossification in collagen X mouse models leads to impaired immune responses. Dev Dyn 237:2693–2704CrossRefPubMed

61.

Jacenko O, Roberts DW, Campbell MR, McManus PM, Gress CJ, Tao Z (2002) Linking hematopoiesis to endochondral skeletogenesis through analysis of mice transgenic for collagen X. Am J Pathol 160:2019–2034PubMed

Title: Growth-plate cartilage in chronic renal failure
Author: Cheryl P. Sanchez
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/s00467-009-1307-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Growth-plate cartilage in chronic renal failure

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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