Skip to main content
SpringerLink
Log in

Growth Plate Research

  • Chapter
  • First Online:
Principles of Bone and Joint Research

Part of the book series: Learning Materials in Biosciences ((LMB))

Abstract

Growth in mammals is a unique and fascinating process which takes place in the growth plates (GP) of long bones and vertebrae.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ahmed SF, Farquharson C. The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins. J Endocrinol. 2010;206:249–59. doi:10.1677/JOE-10-0045.

    Article  CAS  PubMed  Google Scholar 

  2. Albrecht C, Helmreich M, Tichy B, et al. Impact of 3D-culture on the expression of differentiation markers and hormone receptors in growth plate chondrocytes as compared to articular chondrocytes. Int J Mol Med. 2009;23(3):347–55. doi:10.3892/ijmm_00000138.

    CAS  PubMed  Google Scholar 

  3. Atala A, Lanza RP. Methods of tissue engineering. San Diego: Gulf Professional Publishing; 2002.

    Google Scholar 

  4. Ballock RT, O’Keefe RJ. The biology of the growth plate. J Bone Jt Surg. 2003;85:715–26.

    Article  Google Scholar 

  5. Bush PG, Hall AC, Macnicol MF. New insights into function of the growth plate clinical observations, chondrocyte enlargement and a possible role for membrane transporters. J Bone Joint Surg Br. 2008;90:1541–7.

    Article  CAS  PubMed  Google Scholar 

  6. Chagin AS, Sävendahl L. GPR30 estrogen receptor expression in the growth plate declines as puberty progresses. J Clin Endocrinol Metab. 2007a;92:4873–7. doi:10.1210/jc.2007-0814.

    Article  CAS  PubMed  Google Scholar 

  7. Chagin AS, Sävendahl L. Oestrogen receptors and linear bone growth. Acta Paediatr. 2007b;96:1275–9. doi:10.1111/j.1651-2227.2007.00415.x.

    Article  PubMed  Google Scholar 

  8. Cooper KL, Oh S, Sung Y, et al. Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions. Nature. 2013;495:375–8. doi:10.1038/nature11940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dy P, Wang W, Bhattaram P, et al. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell. 2012;22:597–609. doi:10.1016/j.devcel.2011.12.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Egerbacher M, Helmreich M, Rossmanith W, Haeusler G. Estrogen receptor-alpha and estrogen receptor-beta are present in the human growth plate in childhood and adolescence, in identical distribution. Horm Res. 2002;58:99–103.

    CAS  PubMed  Google Scholar 

  11. Finger F, Schörle C, Zien A, et al. Molecular phenotyping of human chondrocyte cell lines T/C-28a2, T/C-28a4, and C-28/I2. Arthritis Rheum. 2003;48:3395–403. doi:10.1002/art.11341.

    Article  CAS  PubMed  Google Scholar 

  12. Gavénis K, Schmidt-Rohlfing B, Mueller-Rath R, et al. In vitro comparison of six different matrix systems for the cultivation of human chondrocytes. Vitro Cell Dev Biol - Anim. 2006;42:159–67. doi:10.1290/0511079.1.

  13. Gebhard S, Hattori T, Bauer E, et al. Specific expression of Cre recombinase in hypertrophic cartilage under the control of a BAC-Col10a1 promoter. Matrix Biol. 2008;27:693–9. doi:10.1016/j.matbio.2008.07.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gevers EF, Hannah MJ, Waters MJ, Robinson ICAF. 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. 2009;150:3627–36. doi:10.1210/en.2008-0985.

    Article  CAS  PubMed  Google Scholar 

  15. Govoni KE, Lee SK, Chung YS, et al. Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice. Physiol Genomics. 2007;30:354–62. doi:10.1152/physiolgenomics.00022.2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Guo F, Han X, Wu Z, et al. ATF6a, a Runx2-activable transcription factor, is a new regulator of chondrocyte hypertrophy. J Cell Sci. 2016;129:717–28. doi:10.1242/jcs.169623.

    Article  CAS  PubMed  Google Scholar 

  17. Haeusler G, Walter I, Helmreich M, Egerbacher M. Localization of matrix Metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation. Calcif Tissue Int. 2005;76:326–35. doi:10.1007/s00223-004-0161-6.

    Article  CAS  PubMed  Google Scholar 

  18. Häusler G, Helmreich M, Marlovits S, Egerbacher M. Integrins and extracellular matrix proteins in the human childhood and adolescent growth plate. Calcif Tissue Int. 2002;71:212–8. doi:10.1007/s00223-001-2083-x.

    Article  PubMed  Google Scholar 

  19. Hunziker EB. Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc Res Tech. 1994;28:505–19.

    Article  CAS  PubMed  Google Scholar 

  20. Hunziker EB, Schenk RK. Cartilage ultrastructure after high pressure freezing, freeze substitution, and low temperature embedding. II Intercellular matrix ultrastructure - preservation of proteoglycans in their native state J Cell Biol. 1984;98:277–82.

    Google Scholar 

  21. Hunziker EB, Herrmann W, Schenk RK. Ruthenium hexammine trichloride (RHT)-mediated interaction between plasmalemmal components and pericellular matrix proteoglycans is responsible for the preservation of chondrocytic plasma membranes in situ during cartilage fixation. J Histochem Cytochem. 1983;31:717–27.

    Article  CAS  PubMed  Google Scholar 

  22. Hunziker EB, Lippuner K, Shintani N. How best to preserve and reveal the structural intricacies of cartilaginous tissue. Matrix Biol. 2014;39C:33–43. doi:10.1016/j.matbio.2014.08.010.

    Article  Google Scholar 

  23. Iwai T, Murai J, Yoshikawa H, Tsumaki N. Smad7 inhibits chondrocyte differentiation at Multiple steps during Endochondral bone formation and down-regulates p38 MAPK pathways. J Biol Chem. 2008;283:27154–64. doi:10.1074/jbc.M801175200.

    Article  CAS  PubMed  Google Scholar 

  24. Jacquet R, Hillyer J, Landis WJ. Analysis of connective tissues by laser capture microdissection and reverse transcriptase-polymerase chain reaction. Anal Biochem. 2005;337:22–34. doi:10.1016/j.ab.2004.09.033.

    Article  CAS  PubMed  Google Scholar 

  25. Kaarniranta K, Ihanamäki T, Sahlman J, et al. A mouse model for Stickler’s syndrome: ocular phenotype of mice carrying a targeted heterozygous inactivation of type II (pro)collagen gene (Col2a1). Exp Eye Res. 2006;83:297–303. doi:10.1016/j.exer.2005.11.027.

    Article  CAS  PubMed  Google Scholar 

  26. Kaplan SA, Cohen P. REVIEW: the Somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab. 2007;92:4529–35. doi:10.1210/jc.2007-0526.

    Article  CAS  PubMed  Google Scholar 

  27. Komori T. Signaling networks in RUNX2-dependent bone development. J Cell Biochem. 2011;112:750–5. doi:10.1002/jcb.22994.

    Article  CAS  PubMed  Google Scholar 

  28. Kronenberg HM. Developmental regulation of the growth plate. Nature. 2003;423:332–6.

    Article  CAS  PubMed  Google Scholar 

  29. Kronenberg HM. PTHrP and Skeletal Development. Ann N Y Acad Sci. 2006;1068:1–13. doi:10.1196/annals.1346.002.

    Article  CAS  PubMed  Google Scholar 

  30. Lango Allen H, Estrada K, Lettre G, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–8. doi:10.1038/nature09410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Le Roith D, Bondy C, Yakar S, et al. The somatomedin hypothesis: 2001. Endocr Rev. 2001;22:53–74.

    Google Scholar 

  32. Liu ES, Raimann A, Chae BT, et al. c-Raf promotes angiogenesis during normal growth plate maturation. Development. 2016;143:348–55. doi:10.1242/dev.127142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Loeser RF, Shanker G. Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediates chondrocyte survival in vitro. Arthritis Rheum. 2000;43:1552–9. doi:10.1002/1529-0131(200007)43:7<1552::AID-ANR20>3.0.CO;2-W.

    Google Scholar 

  34. Loqman MY, Bush PG, Farquharson C, Hall AC. A cell shrinkage artefact in growth plate chondrocytes with common fixative solutions: importance of fixative osmolarity for maintaining morphology. Eur Cell Mater. 2010;14:214–27.

    Article  Google Scholar 

  35. Lui JCK, Andrade AC, Forcinito P, et al. Spatial and temporal regulation of gene expression in the mammalian growth plate. Bone. 2010;46:1380–90. doi:10.1016/j.bone.2010.01.373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mackie EJ, Tatarczuch L, Mirams M. The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification. J Endocrinol. 2011;211:109–21. doi:10.1530/JOE-11-0048.

    Article  CAS  PubMed  Google Scholar 

  37. Mårtensson K, Chrysis D, Sävendahl L. Interleukin-1β and TNF-α act in synergy to inhibit longitudinal growth in Fetal rat metatarsal bones. J Bone Miner Res. 2004;19:1805–12. doi:10.1359/JBMR.040805.

    Article  PubMed  Google Scholar 

  38. Narayana J, Horton WA. FGFR3 biology and skeletal disease. Connect Tissue Res. 2015;56:427–33. doi:10.3109/03008207.2015.1051224.

    Article  CAS  PubMed  Google Scholar 

  39. Nilsson O, Weise M, Landman EBM, et al. Evidence that estrogen hastens epiphyseal fusion and cessation of longitudinal bone growth by irreversibly depleting the number of resting zone progenitor cells in female rabbits. Endocrinology. 2014;155:2892–9. doi:10.1210/en.2013-2175.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Oberbauer AM, Peng R. Fractionation of growth plate chondrocytes: differential expression of IGF-I and growth hormone and IGF-I receptor mRNA in purified populations. Connect Tissue Res. 1995;31:179–87.

    Article  CAS  PubMed  Google Scholar 

  41. Ornitz DM. FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Rev. 2005;16:205–13. doi:10.1016/j.cytogfr.2005.02.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ortega N, Behonick DJ, Werb Z. Matrix remodeling during endochondral ossification. Trends Cell Biol. 2004;14:86–93. doi:10.1016/j.tcb.2003.12.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Parker EA, Hegde A, Buckley M, et al. Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. J Endocrinol. 2007;194:31–40. doi:10.1677/JOE-07-0012.

    Article  CAS  PubMed  Google Scholar 

  44. Sabbagh Y, Carpenter TO, Demay MB. Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci U S A. 2005;102:9637–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Scharmer D. Differential gene expression in chondrocytes of the resting, proliferative and hypertrophic zone of the growth plate in the pig at different stages of development [dissertation]. University of Veterinary Medicine, Vienna, Austria 2009.

    Google Scholar 

  46. Schlegel W, Halbauer D, Raimann A, et al. IGF expression patterns and regulation in growth plate chondrocytes. Mol Cell Endocrinol. 2010;327:65–71. doi:10.1016/j.mce.2010.06.005.

    Article  CAS  PubMed  Google Scholar 

  47. Schlegel W, Raimann A, Halbauer D, et al. Insulin-like growth factor I (IGF-1) Ec/Mechano growth factor – a splice variant of IGF-1 within the growth plate. PLoS One. 2013;8:e76133. doi:10.1371/journal.pone.0076133.

  48. Shao YY, Wang L, Hicks DG, Ballock RT. Analysis of gene expression in mineralized skeletal tissues by laser capture microdissection and RT-PCR. Lab Invest. 2006;86:1089–95. doi:10.1038/labinvest.3700459.

    Article  CAS  PubMed  Google Scholar 

  49. Studer D, Michel M, Wohlwend M, et al. Vitrification of articular cartilage by high-pressure freezing. J Microsc. 1995;179:321–32.

    Article  CAS  PubMed  Google Scholar 

  50. Studer D, Millan C, Oeztuerk E, et al. Molecular and biophysical mechanisms regulating hypertrophic differentiation in chondrocytes and mesenchymal stem cells. Eur Cell Mater. 2012;24:118–35.

    Article  CAS  PubMed  Google Scholar 

  51. Tare RS, Howard D, Pound JC, et al. Tissue engineering strategies for cartilage generation—Micromass and three dimensional cultures using human chondrocytes and a continuous cell line. Biochem Biophys Res Commun. 2005;333:609–21. doi:10.1016/j.bbrc.2005.05.117.

    Article  CAS  PubMed  Google Scholar 

  52. Wang JIE, ZHOU J, BONDY CA. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J. 1999;13:1985–90.

    CAS  PubMed  Google Scholar 

  53. Wang Y, Spatz MK, Kannan K, et al. A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3. Proc Natl Acad Sci. 1999;96:4455–60. doi:10.1073/pnas.96.8.4455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang W, Rigueur D, Lyons KM. TGFβ signaling in cartilage development and maintenance. Birth Defects Res Part C Embryo Today. 2014;102:37–51. doi:10.1002/bdrc.21058.

    Article  CAS  Google Scholar 

  55. Wit JM, Camacho-Hübner C. Endocrine regulation of longitudinal bone growth. Endocr Dev. 2011;21:30–41. doi:10.1159/000328119.

    Article  CAS  PubMed  Google Scholar 

  56. Yao Y, Wang Y. ATDC5: An excellent in vitro model cell line for skeletal development. J Cell Biochem. 2013;114:1223–9. doi:10.1002/jcb.24467.

  57. Zhai Z, Yao Y, Wang Y. Importance of suitable reference Gene selection for quantitative RT-PCR during ATDC5 cells chondrocyte differentiation. PLoS One. 2013;8:e64786. doi:10.1371/journal.pone.0064786.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Clinic of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

    Gabriele Haeusler & Adalbert Raimann

  2. Veterinary University Vienna, Institute of Anatomy, Histology and Embryology, Vienna, Austria

    Monika Egerbacher

Authors
  1. Gabriele Haeusler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adalbert Raimann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika Egerbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriele Haeusler .

Editor information

Editors and Affiliations

  1. Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Haeusler, G., Raimann, A., Egerbacher, M. (2017). Growth Plate Research. In: Pietschmann, P. (eds) Principles of Bone and Joint Research. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-319-58955-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation