Skip to main content
SpringerLink
Log in
Book cover

Cartilage pp 83–113Cite as

The Cartilaginous Growth Plate

  • Chapter
  • First Online:

Abstract

The cartilaginous growth plate is a well-organized and highly specialized tissue which drives the longitudinal elongation of bones developing through endochondral bone formation. A tightly regulated differentiation program of chondrocyte proliferation, maturation, and hypertrophy associated with extracellular matrix production, mineralization, and degradation culminates in the replacement of cartilage with bone. Chondrocytes within the growth plate are organized into anatomically well-defined horizontal zones, which reflect their morphologically, biochemically, and transcriptionally distinct differentiation stages. The differentiation process is accompanied by the establishment of cellular anisotropy and planar polarity that generates the unique spatial structure of the tissue. Proliferative chondrocytes acquire an elongated shape, align and divide orthogonally to the direction of the growth, and arrange into vertical columns that in most vertebrates direct the elongation process. Chondrocyte differentiation and polarity are essential and mutually interacting foundations of the normal growth pate function, and their disturbance results in chondrodysplasias with impaired longitudinal growth. This chapter will focus on the mechanisms responsible for the establishment and maintenance of the structural polarity of the cartilaginous growth plate.

This is a preview of subscription content, 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   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

References

  • 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(5):1851–1857

    Article  CAS  PubMed  Google Scholar 

  • Ahrens MJ, Li Y, Jiang H, Dudley AT (2009) Convergent extension movements in growth plate chondrocytes require gpi-anchored cell surface proteins. Development 136(20):3463–3474. doi:10.1242/dev.040592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y (1999) Perlecan is essential for cartilage and cephalic development. Nat Genet 23(3):354–358. doi:10.1038/15537

    Article  CAS  PubMed  Google Scholar 

  • Aro E, Salo AM, Khatri R, Finnila M, Miinalainen I, Sormunen R, Pakkanen O, Holster T, Soininen R, Prein C, Clausen-Schaumann H, Aszodi A, Tuukkanen J, Kivirikko KI, Schipani E, Myllyharju J (2015) Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I. J Biol Chem 290(27):16964–16978. doi:10.1074/jbc.M115.662635

    Article  CAS  PubMed  Google Scholar 

  • Ascenzi MG, Lenox M, Farnum C (2007) Analysis of the orientation of primary cilia in growth plate cartilage: a mathematical method based on multiphoton microscopical images. J Struct Biol 158(3):293–306. doi:10.1016/j.jsb.2006.11.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ascenzi MG, Blanco C, Drayer I, Kim H, Wilson R, Retting KN, Lyons KM, Mohler G (2011) Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization. J Theor Biol 285(1):147–155. doi:10.1016/j.jtbi.2011.06.016

    Article  PubMed  PubMed Central  Google Scholar 

  • Aszodi A, Chan D, Hunziker E, Bateman JF, Fassler R (1998) Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol 143(5):1399–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aszodi A, Hunziker EB, Brakebusch C, Fassler R (2003) Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis. Genes Dev 17(19):2465–2479. doi:10.1101/gad.277003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bader DL, Salter DM, Chowdhury TT (2011) Biomechanical influence of cartilage homeostasis in health and disease. Arthritis 2011:979032. doi:10.1155/2011/979032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballock RT, O’Keefe RJ (2003) The biology of the growth plate. J Bone Joint Surg Am 85-A:715–726

    PubMed  Google Scholar 

  • Bengtsson T, Aszodi A, Nicolae C, Hunziker EB, Lundgren-Akerlund E, Fassler R (2005) Loss of alpha10beta1 integrin expression leads to moderate dysfunction of growth plate chondrocytes. J Cell Sci 118(Pt 5):929–936. doi:10.1242/jcs.01678

    Article  CAS  PubMed  Google Scholar 

  • Blumbach K, Niehoff A, Paulsson M, Zaucke F (2008) Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture. Matrix Biol 27(4):306–318. doi:10.1016/j.matbio.2007.11.007

    Article  CAS  PubMed  Google Scholar 

  • Breur GJ, VanEnkevort BA, Farnum CE, Wilsman NJ (1991) Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. J Orthop Res 9(3):348–359. doi:10.1002/jor.1100090306

    Article  CAS  PubMed  Google Scholar 

  • Brighton CT (1978) Structure and function of the growth plate. Clin Orthop Relat Res 136:22–32

    PubMed  Google Scholar 

  • Candela ME, Cantley L, Yasuaha R, Iwamoto M, Pacifici M, Enomoto-Iwamoto M (2014) Distribution of slow-cycling cells in epiphyseal cartilage and requirement of beta-catenin signaling for their maintenance in growth plate. J Orthop Res 32(5):661–668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chagin AS, Vuppalapati KK, Kobayashi T, Guo J, Hirai T, Chen M, Offermanns S, Weinstein LS, Kronenberg HM (2014) G-protein stimulatory subunit alpha and Gq/11alpha G-proteins are both required to maintain quiescent stem-like chondrocytes. Nat Commun 5(3673)

    Google Scholar 

  • Chan D, Cole WG, Chow CW, Mundlos S, Bateman JF (1995) A COL2A1 mutation in achondrogenesis type II results in the replacement of type II collagen by type I and III collagens in cartilage. J Biol Chem 270(4):1747–1753

    Article  CAS  PubMed  Google Scholar 

  • Chang CF, Serra R (2013) Ift88 regulates Hedgehog signaling, Sfrp5 expression, and beta-catenin activity in post-natal growth plate. J Orthop Res 31(3):350–356. doi:10.1002/jor.22237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang R, Petersen JR, Niswander LA, Liu A (2015) A hypomorphic allele reveals an important role of inturned in mouse skeletal development. Dev Dyn 244(6):736–747. doi:10.1002/dvdy.24272

    Article  PubMed  Google Scholar 

  • Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R (1999) Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147(5):1109–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Andrea CE, Wiweger M, Prins F, Bovee JV, Romeo S, Hogendoorn PC (2010) Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma. Lab Invest 90(7):1091–1101. doi:10.1038/labinvest.2010.81

    Article  PubMed  Google Scholar 

  • DeChiara TM, Kimble RB, Poueymirou WT, Rojas J, Masiakowski P, Valenzuela DM, Yancopoulos GD (2000) Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development. Nat Genet 24(3):271–274. doi:10.1038/73488

    Article  CAS  PubMed  Google Scholar 

  • Dell’Orbo C, Gioglio L, Quacci D (1992) Morphology of epiphyseal apparatus of a ranid frog (Rana Esculenta). Histol Histopathol 7(2):267–273

    PubMed  Google Scholar 

  • Devenport D (2014) The cell biology of planar cell polarity. J Cell Biol 207(2):171–179. doi:10.1083/jcb.201408039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dodds GS (1930) Row formation and other types of arrangement of cartilage cells in endochondral ossification. Anat Rec 46(4):385–399. doi:10.1002/ar.1090460409

    Article  Google Scholar 

  • Dreier R, Opolka A, Grifka J, Bruckner P, Grassel S (2008) Collagen IX-deficiency seriously compromises growth cartilage development in mice. Matrix Biol 27(4):319–329. doi:10.1016/j.matbio.2008.01.006

    Article  CAS  PubMed  Google Scholar 

  • Eggli PS, Herrmann W, Hunziker EB, Schenk RK (1985) Matrix compartments in the growth plate of the proximal tibia of rats. Anat Rec 211(3):246–257. doi:10.1002/ar.1092110304

    Article  CAS  PubMed  Google Scholar 

  • Eisenstein R, Sorgente N, Kuettner KE (1971) Organization of extracellular matrix in epiphyseal growth plate. Am J Pathol 65(3):515–534

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farnum CE, Wilsman NJ (1993) Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine. Calcif Tissue Int 52(2):110–119

    Article  CAS  PubMed  Google Scholar 

  • Farquharson C, Jefferies D (2000) Chondrocytes and longitudinal bone growth: the development of tibial dyschondroplasia. Poult Sci 79(7):994–1004

    Article  CAS  PubMed  Google Scholar 

  • Felisbino SL, Carvalho HF (2001) Growth cartilage calcification and formation of bone trabeculae are late and dissociated events in the endochondral ossification of Rana catesbeiana. Cell Tissue Res 306(2):319–323

    Article  CAS  PubMed  Google Scholar 

  • Fenichel I, Evron Z, Nevo Z (2006) The perichondrial ring as a reservoir for precartilaginous cells. In vivo model in young chicks’ epiphysis. Int Orthop 30(5):353–356

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao B, Yang Y (2013) Planar cell polarity in vertebrate limb morphogenesis. Curr Opin Genet Dev 23(4):438–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao B, Song H, Bishop K, Elliot G, Garrett L, English MA, Andre P, Robinson J, Sood R, Minami Y, Economides AN, Yang Y (2011) Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Dev Cell 20(2):163–176. doi:10.1016/j.devcel.2011.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geister KA, Brinkmeier ML, Cheung LY, Wendt J, Oatley MJ, Burgess DL, Kozloff KM, Cavalcoli JD, Oatley JM, Camper SA (2015) LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice. PLoS Genet 11(10):e1005569. doi:10.1371/journal.pgen.1005569

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Germiller JA, Goldstein SA (1997) Structure and function of embryonic growth plate in the absence of functioning skeletal muscle. J Orthop Res 15(3):362–370. doi:10.1002/jor.1100150308

    Article  CAS  PubMed  Google Scholar 

  • Ghatak S, Morgner J, Wickstrom SA (2013) ILK: a pseudokinase with a unique function in the integrin-actin linkage. Biochem Soc Trans 41(4):995–1001. doi:10.1042/bst20130062

    Article  CAS  PubMed  Google Scholar 

  • Gould RP, Selwood L, Day A, Wolpert L (1974) The mechanism of cellular orientation during early cartilage formation in the chick limb and regenerating amphibian limb. Exp Cell Res 83(2):287–296

    Article  CAS  PubMed  Google Scholar 

  • Grashoff C, Aszodi A, Sakai T, Hunziker EB, Fassler R (2003) Integrin-linked kinase regulates chondrocyte shape and proliferation. EMBO Rep 4(4):432–438. doi:10.1038/sj.embor.embor801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall BK, Herring SW (1990) Paralysis and growth of the musculoskeletal system in the embryonic chick. J Morphol 206(1):45–56. doi:10.1002/jmor.1052060105

    Article  CAS  PubMed  Google Scholar 

  • Haycraft CJ, Serra R (2008) Cilia involvement in patterning and maintenance of the skeleton. Curr Top Dev Biol 85:303–332. doi:10.1016/s0070-2153(08)00811-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haycraft CJ, Zhang Q, Song B, Jackson WS, Detloff PJ, Serra R, Yoder BK (2007) Intraflagellar transport is essential for endochondral bone formation. Development 134(2):307–316. doi:10.1242/dev.02732

    Article  CAS  PubMed  Google Scholar 

  • Heisenberg CP, Bellaiche Y (2013) Forces in tissue morphogenesis and patterning. Cell 153(5):948–962

    Article  CAS  PubMed  Google Scholar 

  • Hertwig O (1893) Ueber den Werth der ersten Furchungszellen für die Organbildung des Embryo Experimentelle Studien am Frosch-und Tritonei. Archiv f mikrosk Anat 42(4):662–807. doi:10.1007/BF02976796

    Article  Google Scholar 

  • Hiraoka S, Furuichi T, Nishimura G, Shibata S, Yanagishita M, Rimoin DL, Superti-Furga A, Nikkels PG, Ogawa M, Katsuyama K, Toyoda H, Kinoshita-Toyoda A, Ishida N, Isono K, Sanai Y, Cohn DH, Koseki H, Ikegawa S (2007) Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. Nat Med 13(11):1363–1367. doi:10.1038/nm1655

    Article  CAS  PubMed  Google Scholar 

  • Holmes LB, Trelstad RL (1980) Cell polarity in precartilage mouse limb mesenchyme cells. Dev Biol 78(2):511–520

    Article  CAS  PubMed  Google Scholar 

  • Hosseini A, Hogg DA (1991a) The effects of paralysis on skeletal development in the chick embryo. I General effects. J Anat 177:159–168

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hosseini A, Hogg DA (1991b) The effects of paralysis on skeletal development in the chick embryo. II. Effects on histogenesis of the tibia. J Anat 177:169–178

    CAS  PubMed  PubMed Central  Google Scholar 

  • Howlett CR (1979) The fine structure of the proximal growth plate of the avian tibia. J Anat 128(Pt 2):377–399

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hunziker EB (1994) Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc Res Tech 28(6):505–519. doi:10.1002/jemt.1070280606

    Article  CAS  PubMed  Google Scholar 

  • Hunziker EB, Schenk RK (1989) Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats. J Physiol 414:55–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunziker EB, Schenk RK, Cruz-Orive LM (1987) Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone growth. J Bone Joint Surg Am 69(2):162–173

    CAS  PubMed  Google Scholar 

  • Hunziker EB, Wagner J, Studer D (1996) Vitrified articular cartilage reveals novel ultra-structural features respecting extracellular matrix architecture. Histochem Cell Biol 106(4):375–382

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ilharreborde B, Raquillet C, Morel E, Fitoussi F, Bensahel H, Pennecot GF, Mazda K (2006) Long-term prognosis of Salter-Harris type 2 injuries of the distal femoral physis. J Pediatr Orthop B 15(6):433–438. doi:10.1097/01.bpb.0000228384.01690.aa

    Article  PubMed  Google Scholar 

  • Jensen CG, Poole CA, McGlashan SR, Marko M, Issa ZI, Vujcich KV, Bowser SS (2004) Ultrastructural, tomographic and confocal imaging of the chondrocyte primary cilium in situ. Cell Biol Int 28(2):101–110. doi:10.1016/j.cellbi.2003.11.007

    Article  CAS  PubMed  Google Scholar 

  • Johnstone EW, Leane PB, Kolesik P, Byers S, Foster BK (2000) Spatial arrangement of physeal cartilage chondrocytes and the structure of the primary spongiosa. J Orthop Sci 5(3):294–301. doi:10.1007/s007760000050294.776

    Article  CAS  PubMed  Google Scholar 

  • Kamper M, Hamann N, Prein C, Clausen-Schaumann H, Farkas Z, Aszodi A, Niehoff A, Paulsson M, Zaucke F (2015) Early changes in morphology, bone mineral density and matrix composition of vertebrae lead to disc degeneration in aged collagen IX -/- mice. Matrix Biol. doi:10.1016/j.matbio.2015.09.005

    PubMed  Google Scholar 

  • Karlsson C, Thornemo M, Henriksson HB, Lindahl A (2009) Identification of a stem cell niche in the zone of Ranvier within the knee joint. J Anat 215(3):355–363

    Article  PubMed  PubMed Central  Google Scholar 

  • Kato K, Bhattaram P, Penzo-Mendez A, Gadi A, Lefebvre V (2015) SOXC transcription factors induce cartilage growth plate formation in mouse embryos by promoting noncanonical WNT signaling. J Bone Miner Res 30(9):1560–1571. doi:10.1002/jbmr.2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keller R, Davidson L, Edlund A, Elul T, Ezin M, Shook D, Skoglund P (2000) Mechanisms of convergence and extension by cell intercalation. Philos Trans R Soc Lond B Biol Sci 355(1399):897–922. doi:10.1098/rstb.2000.0626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kember NF (1971) Cell population kinetics of bone growth: the first ten years of autoradiographic studies with tritiated thymidine. Clin Orthop Relat Res 76:213–230

    Article  CAS  PubMed  Google Scholar 

  • Kember NF, Kirkwood JK, Duignan PJ, Godfrey D, Spratt DJ (1990) Comparative cell kinetics of avian growth plates. Res Vet Sci 49(3):283–288

    CAS  PubMed  Google Scholar 

  • Kimmel CB, Miller CT, Kruze G, Ullmann B, BreMiller RA, Larison KD, Snyder HC (1998) The shaping of pharyngeal cartilages during early development of the zebrafish. Dev Biol 203(2):245–263. doi:10.1006/dbio.1998.9016

    Article  CAS  PubMed  Google Scholar 

  • Kluppel M, Wight TN, Chan C, Hinek A, Wrana JL (2005) Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development 132(17):3989–4003. doi:10.1242/dev.01948

    Article  CAS  PubMed  Google Scholar 

  • Knight MM, McGlashan SR, Garcia M, Jensen CG, Poole CA (2009) Articular chondrocytes express connexin 43 hemichannels and P2 receptors – a putative mechanoreceptor complex involving the primary cilium? J Anat 214(2):275–283. doi:10.1111/j.1469-7580.2008.01021.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolpakova-Hart E, Jinnin M, Hou B, Fukai N, Olsen BR (2007) Kinesin-2 controls development and patterning of the vertebrate skeleton by Hedgehog- and Gli3-dependent mechanisms. Dev Biol 309(2):273–284. doi:10.1016/j.ydbio.2007.07.018

    Article  CAS  PubMed  Google Scholar 

  • Koziel L, Kunath M, Kelly OG, Vortkamp A (2004) Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev Cell 6(6):801–813. doi:10.1016/j.devcel.2004.05.009

    Article  CAS  PubMed  Google Scholar 

  • Krueger RC Jr, Kurima K, Schwartz NB (1999) Completion of the mouse aggrecan gene structure and identification of the defect in the cmd-Bc mouse as a near complete deletion of the murine aggrecan gene. Mamm Genome 10(12):1119–1125

    Article  CAS  PubMed  Google Scholar 

  • Kuss P, Kraft K, Stumm J, Ibrahim D, Vallecillo-Garcia P, Mundlos S, Stricker S (2014) Regulation of cell polarity in the cartilage growth plate and perichondrium of metacarpal elements by HOXD13 and WNT5A. Dev Biol 385(1):83–93. doi:10.1016/j.ydbio.2013.10.013

    Article  CAS  PubMed  Google Scholar 

  • Kyostila K, Lappalainen AK, Lohi H (2013) Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. PLoS One 8(9):e75621. doi:10.1371/journal.pone.0075621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langenskiold A (1998) Role of the ossification groove of Ranvier in normal and pathologic bone growth: a review. J Pediatr Orthop 18(2):173–177

    CAS  PubMed  Google Scholar 

  • Lauing KL, Cortes M, Domowicz MS, Henry JG, Baria AT, Schwartz NB (2014) Aggrecan is required for growth plate cytoarchitecture and differentiation. Dev Biol 396(2):224–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefebvre V, Bhattaram P (2010) Vertebrate skeletogenesis. Curr Top Dev Biol 90:291–317

    Article  PubMed  PubMed Central  Google Scholar 

  • Legate KR, Wickstrom SA, Fassler R (2009) Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev 23(4):397–418. doi:10.1101/gad.1758709, 23/4/397 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Dudley AT (2009) Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes. Development 136(7):1083–1092. doi:10.1242/dev.023820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li SW, Prockop DJ, Helminen H, Fassler R, Lapvetelainen T, Kiraly K, Peltarri A, Arokoski J, Lui H, Arita M et al (1995a) Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone. Genes Dev 9(22):2821–2830

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Lacerda DA, Warman ML, Beier DR, Yoshioka H, Ninomiya Y, Oxford JT, Morris NP, Andrikopoulos K, Ramirez F et al (1995b) A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis. Cell 80(3):423–430

    Article  CAS  PubMed  Google Scholar 

  • Lui JC, Nilsson O, Chan Y, Palmer CD, Andrade AC, Hirschhorn JN, Baron J (2012) Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height. Hum Mol Genet 21(23):5193–5201. doi:10.1093/hmg/dds347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marlow F, Zwartkruis F, Malicki J, Neuhauss SC, Abbas L, Weaver M, Driever W, Solnica-Krezel L (1998) Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish. Dev Biol 203(2):382–399. doi:10.1006/dbio.1998.9032

    Article  CAS  PubMed  Google Scholar 

  • McGlashan SR, Jensen CG, Poole CA (2006) Localization of extracellular matrix receptors on the chondrocyte primary cilium. J Histochem Cytochem 54(9):1005–1014. doi:10.1369/jhc.5A6866.2006

    Article  CAS  PubMed  Google Scholar 

  • McGlashan SR, Haycraft CJ, Jensen CG, Yoder BK, Poole CA (2007) Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737orpk mice lacking the primary cilia protein polaris. Matrix Biol 26(4):234–246. doi:10.1016/j.matbio.2006.12.003

    Article  CAS  PubMed  Google Scholar 

  • McGlashan SR, Knight MM, Chowdhury TT, Joshi P, Jensen CG, Kennedy S, Poole CA (2010) Mechanical loading modulates chondrocyte primary cilia incidence and length. Cell Biol Int 34(5):441–446. doi:10.1042/cbi20090094

    Article  PubMed  Google Scholar 

  • Meves A, Stremmel C, Gottschalk K, Fassler R (2009) The Kindlin protein family: new members to the club of focal adhesion proteins. Trends Cell Biol 19(10):504–513. doi:10.1016/j.tcb.2009.07.006

    Article  CAS  PubMed  Google Scholar 

  • Mizumoto S, Yamada S, Sugahara K (2014) Human genetic disorders and knockout mice deficient in glycosaminoglycan. Biomed Res Int 2014:495764. doi:10.1155/2014/495764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Muhammad H, Rais Y, Miosge N, Ornan EM (2012) The primary cilium as a dual sensor of mechanochemical signals in chondrocytes. Cell Mol Life Sci 69(13):2101–2107. doi:10.1007/s00018-011-0911-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson WJ (2008) Regulation of cell-cell adhesion by the cadherin-catenin complex. Biochem Soc Trans 36(Pt 2):149–155. doi:10.1042/bst0360149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicolae C, Ko YP, Miosge N, Niehoff A, Studer D, Enggist L, Hunziker EB, Paulsson M, Wagener R, Aszodi A (2007) Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice. J Biol Chem 282(30):22163–22175. doi:10.1074/jbc.M610994200

    Article  CAS  PubMed  Google Scholar 

  • Nowlan NC, Bourdon C, Dumas G, Tajbakhsh S, Prendergast PJ, Murphy P (2010) Developing bones are differentially affected by compromised skeletal muscle formation. Bone 46(5):1275–1285. doi:10.1016/j.bone.2009.11.026

    Article  PubMed  PubMed Central  Google Scholar 

  • Ochiai T, Nagayama M, Nakamura T, Morrison T, Pilchak D, Kondo N, Hasegawa H, Song B, Serra R, Pacifici M, Koyama E (2009) Roles of the primary cilium component Polaris in synchondrosis development. J Dent Res 88(6):545–550. doi:10.1177/0022034509337775

    Article  CAS  PubMed  Google Scholar 

  • Ohlsson C, Nilsson A, Isaksson O, Lindahl A (1992) Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc Natl Acad Sci U S A 89(20):9826–9830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oro AE (2007) The primary cilia, a ‘Rab-id’ transit system for hedgehog signaling. Curr Opin Cell Biol 19(6):691–696. doi:10.1016/j.ceb.2007.10.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ortega N, Behonick DJ, Werb Z (2004) Matrix remodeling during endochondral ossification. Trends Cell Biol 14(2):86–93. doi:10.1016/j.tcb.2003.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park TJ, Haigo SL, Wallingford JB (2006) Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Nat Genet 38(3):303–311. doi:10.1038/ng1753

    Article  CAS  PubMed  Google Scholar 

  • Park J, Gebhardt M, Golovchenko S, Perez-Branguli F, Hattori T, Hartmann C, Zhou X, deCrombrugghe B, Stock M, Schneider H, von der Mark K (2015) Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage. Biol Open 4(5):608–621

    Article  PubMed  PubMed Central  Google Scholar 

  • Parr BA, Shea MJ, Vassileva G, McMahon AP (1993) Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119(1):247–261

    CAS  PubMed  Google Scholar 

  • Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, Fassler R, Kallio M, Ivaska J (2008) Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell 15(3):371–385. doi:10.1016/j.devcel.2008.08.001

    Article  CAS  PubMed  Google Scholar 

  • Peltomaki T, Hakkinen L (1992) Growth of the ribs at the costochondral junction in the rat. J Anat 181(Pt 2):259–264

    PubMed  PubMed Central  Google Scholar 

  • Phan MN, Leddy HA, Votta BJ, Kumar S, Levy DS, Lipshutz DB, Lee SH, Liedtke W, Guilak F (2009) Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum 60(10):3028–3037. doi:10.1002/art.24799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piotrowski T, Schilling TF, Brand M, Jiang YJ, Heisenberg CP, Beuchle D, Grandel H, van Eeden FJ, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane DA, Kelsh RN, Mullins MC, Odenthal J, Warga RM, Nusslein-Volhard C (1996) Jaw and branchial arch mutants in zebrafish II: anterior arches and cartilage differentiation. Development 123:345–356

    CAS  PubMed  Google Scholar 

  • Poole CA, Jensen CG, Snyder JA, Gray CG, Hermanutz VL, Wheatley DN (1997) Confocal analysis of primary cilia structure and colocalization with the Golgi apparatus in chondrocytes and aortic smooth muscle cells. Cell Biol Int 21(8):483–494. doi:10.1006/cbir.1997.0177

    Article  CAS  PubMed  Google Scholar 

  • Posey KL, Hankenson K, Veerisetty AC, Bornstein P, Lawler J, Hecht JT (2008) Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1, thrombospondin-3, thrombospondin-5, and type IX collagen. Am J Pathol 172(6):1664–1674. doi:10.2353/ajpath.2008.071094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad RM, Jin X, Nauli SM (2014) Sensing a sensor: identifying the mechanosensory function of primary cilia. Biosensors 4(1):47–62. doi:10.3390/bios4010047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prein C, Warmbold N, Farkas Z, Schieker M, Aszodi A, Clausen-Schaumann H (2015) Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy. Matrix Biol. doi:10.1016/j.matbio.2015.10.001

    Google Scholar 

  • Raducanu A, Hunziker EB, Drosse I, Aszodi A (2009) Beta1 integrin deficiency results in multiple abnormalities of the knee joint. J Biol Chem 284(35):23780–23792. doi:10.1074/jbc.M109.039347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randall RM, Shao YY, Wang L, Ballock RT (2012) Activation of Wnt Planar Cell Polarity (PCP) signaling promotes growth plate column formation in vitro. J Orthop Res 30(12):1906–1914. doi:10.1002/jor.22152

    Article  CAS  PubMed  Google Scholar 

  • Riseborough EJ, Barrett IR, Shapiro F (1983) Growth disturbances following distal femoral physeal fracture-separations. J Bone Joint Surg Am 65(7):885–893

    CAS  PubMed  Google Scholar 

  • Robbins DJ, Fei DL, Riobo NA (2012) The Hedgehog signal transduction network. Sci Signal 5(246):re6. doi:10.1126/scisignal.2002906

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Robinson D, Hasharoni A, Cohen N, Yayon A, Moskowitz RM, Nevo Z (1999) Fibroblast growth factor receptor-3 as a marker for precartilaginous stem cells. Clin Orthop Relat Res 367 Suppl:S163–S175

    Google Scholar 

  • Roddy KA, Prendergast PJ, Murphy P (2011) Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos. PLoS One 6(2):e17526. doi:10.1371/journal.pone.0017526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez JI, Delgado E, Paniagua R (1985) Changes in young rat radius following excision of the perichondrial ring. Calcif Tissue Int 37(6):677–683

    Article  CAS  PubMed  Google Scholar 

  • Romereim SM, Dudley AT (2011) Cell polarity: the missing link in skeletal morphogenesis? Organogenesis 7(3):217–228

    Article  PubMed  PubMed Central  Google Scholar 

  • Romereim SM, Conoan NH, Chen B, Dudley AT (2014) A dynamic cell adhesion surface regulates tissue architecture in growth plate cartilage. Development 141(10):2085–2095. doi:10.1242/dev.105452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rot-Nikcevic I, Reddy T, Downing KJ, Belliveau AC, Hallgrimsson B, Hall BK, Kablar B (2006) Myf5-/- : MyoD-/- amyogenic fetuses reveal the importance of early contraction and static loading by striated muscle in mouse skeletogenesis. Dev Genes Evol 216(1):1–9. doi:10.1007/s00427-005-0024-9

    Article  PubMed  Google Scholar 

  • Sampson HW, Dearman AC, Akintola AD, Zimmer WE, Parrish AR (2007) Immunohistochemical localization of cadherin and catenin adhesion molecules in the murine growth plate. J Histochem Cytochem 55(8):845–852. doi:10.1369/jhc.7A7184.2007

    Article  CAS  PubMed  Google Scholar 

  • Shao YY, Wang L, Welter JF, Ballock RT (2012) Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes. Bone 50(1):79–84. doi:10.1016/j.bone.2011.08.033

    Article  CAS  PubMed  Google Scholar 

  • Shapiro F, Holtrop ME, Glimcher MJ (1977) Organization and cellular biology of the perichondrial ossification groove of ranvier: a morphological study in rabbits. J Bone Joint Surg Am 59(6):703–723

    CAS  PubMed  Google Scholar 

  • Shea CA, Rolfe RA, Murphy P (2015) The importance of foetal movement for co-ordinated cartilage and bone development in utero : clinical consequences and potential for therapy. Bone Joint Res 4(7):105–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shwartz Y, Farkas Z, Stern T, Aszodi A, Zelzer E (2012) Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension. Dev Biol 370(1):154–163. doi:10.1016/j.ydbio.2012.07.026

    Article  CAS  PubMed  Google Scholar 

  • Song B, Haycraft CJ, Seo HS, Yoder BK, Serra R (2007) Development of the post-natal growth plate requires intraflagellar transport proteins. Dev Biol 305(1):202–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • St-Jacques B, Hammerschmidt M, McMahon AP (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 13(16):2072–2086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki W, Yamada A, Aizawa R, Suzuki D, Kassai H, Harada T, Nakayama M, Nagahama R, Maki K, Takeda S, Yamamoto M, Aiba A, Baba K, Kamijo R (2015) Cdc42 is critical for cartilage development during endochondral ossification. Endocrinology 156(1):314–322. doi:10.1210/en.2014-1032

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi S, Takeda K, Oishi I, Nomi M, Ikeya M, Itoh K, Tamura S, Ueda T, Hatta T, Otani H, Terashima T, Takada S, Yamamura H, Akira S, Minami Y (2000) Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation. Genes Cells 5(1):71–78

    Article  CAS  PubMed  Google Scholar 

  • Talts JF, Pfeifer A, Hofmann F, Hunziker EB, Zhou XH, Aszodi A, Fassler R (1998) Endochondral ossification is dependent on the mechanical properties of cartilage tissue and on intracellular signals in chondrocytes. Ann N Y Acad Sci 857:74–85

    Article  CAS  PubMed  Google Scholar 

  • Terpstra L, Prud’homme J, Arabian A, Takeda S, Karsenty G, Dedhar S, St-Arnaud R (2003) Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes. J Cell Biol 162(1):139–148. doi:10.1083/jcb.200302066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson CL, Chapple JP, Knight MM (2014) Primary cilia disassembly down-regulates mechanosensitive hedgehog signalling: a feedback mechanism controlling ADAMTS-5 expression in chondrocytes. Osteoarthritis Cartilage 22(3):490–498. doi:10.1016/j.joca.2013.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Topczewski J, Sepich DS, Myers DC, Walker C, Amores A, Lele Z, Hammerschmidt M, Postlethwait J, Solnica-Krezel L (2001) The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension. Dev Cell 1(2):251–264

    Article  CAS  PubMed  Google Scholar 

  • Trelstad RL (1977) Mesenchymal cell polarity and morphogenesis of chick cartilage. Dev Biol 59(2):153–163

    Article  CAS  PubMed  Google Scholar 

  • Vanky P, Brockstedt U, Hjerpe A, Wikstrom B (1998) Kinetic studies on epiphyseal growth cartilage in the normal mouse. Bone 22(4):331–339

    Article  CAS  PubMed  Google Scholar 

  • Walzer SM, Cetin E, Grubl-Barabas R, Sulzbacher I, Rueger B, Girsch W, Toegel S, Windhager R, Fischer MB (2014) Vascularization of primary and secondary ossification centres in the human growth plate. BMC Dev Biol 14(36):014–0036

    Google Scholar 

  • Wang X, Mao JJ (2002) Chondrocyte proliferation of the cranial base cartilage upon in vivo mechanical stresses. J Dent Res 81(10):701–705

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Nathans J (2007) Tissue/planar cell polarity in vertebrates: new insights and new questions. Development 134(4):647–658. doi:10.1242/dev.02772

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Woods A, Agoston H, Ulici V, Glogauer M, Beier F (2007) Genetic ablation of Rac1 in cartilage results in chondrodysplasia. Dev Biol 306(2):612–623. doi:10.1016/j.ydbio.2007.03.520

    Article  CAS  PubMed  Google Scholar 

  • Wann AK, Zuo N, Haycraft CJ, Jensen CG, Poole CA, McGlashan SR, Knight MM (2012) Primary cilia mediate mechanotransduction through control of ATP-induced Ca2+ signaling in compressed chondrocytes. FASEB J 26(4):1663–1671. doi:10.1096/fj.11-193649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A(5):943–968. doi:10.1002/ajmg.a.33909

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Yamada Y (1999) Mice lacking link protein develop dwarfism and craniofacial abnormalities. Nat Genet 21(2):225–229. doi:10.1038/6016

    Article  CAS  PubMed  Google Scholar 

  • Watanabe H, Kimata K, Line S, Strong D, Gao LY, Kozak CA, Yamada Y (1994) Mouse cartilage matrix deficiency (cmd) caused by a 7 bp deletion in the aggrecan gene. Nat Genet 7(2):154–157. doi:10.1038/ng0694-154

    Article  CAS  PubMed  Google Scholar 

  • Wilsman NJ, Farnum CE, Green EM, Lieferman EM, Clayton MK (1996a) Cell cycle analysis of proliferative zone chondrocytes in growth plates elongating at different rates. J Orthop Res 14(4):562–572. doi:10.1002/jor.1100140410

    Article  CAS  PubMed  Google Scholar 

  • Wilsman NJ, Farnum CE, Leiferman EM, Fry M, Barreto C (1996b) Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J Orthop Res 14(6):927–936. doi:10.1002/jor.1100140613

    Article  CAS  PubMed  Google Scholar 

  • Wu QQ, Chen Q (2000) Mechanoregulation of chondrocyte proliferation, maturation, and hypertrophy: ion-channel dependent transduction of matrix deformation signals. Exp Cell Res 256(2):383–391. doi:10.1006/excr.2000.4847

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Jiao H, Lai Y, Zheng W, Chen K, Qu H, Deng W, Song P, Zhu K, Cao H, Galson DL, Fan J, Im HJ, Liu Y, Chen J, Chen D, Xiao G (2015) Kindlin-2 controls TGF-beta signalling and Sox9 expression to regulate chondrogenesis. Nat Commun 6(7531)

    Google Scholar 

  • Yamaguchi TP, Bradley A, McMahon AP, Jones S (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126(6):1211–1223

    CAS  PubMed  Google Scholar 

  • Yang Y, Mlodzik M (2015) Wnt-Frizzled/Planar Cell Polarity Signaling: Cellular Orientation by Facing the Wind (Wnt). Annu Rev Cell Dev Biol 31:623–646. doi:10.1146/annurev-cellbio-100814-125315

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Topol L, Lee H, Wu J (2003) Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130(5):1003–1015

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Tsang KY, Tang HC, Chan D, Cheah KS (2014) Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci U S A 111(33):12097–12102. doi:10.1073/pnas.1302703111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan X, Yang S (2015) Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation. PLoS One 10(6):e0130618. doi:10.1371/journal.pone.0130618

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuan X, Serra RA, Yang S (2015) Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton. Ann N Y Acad Sci 1335:78–99. doi:10.1111/nyas.12463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B (2014) Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet 10(12):e1004820. doi:10.1371/journal.pgen.1004820

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Surgery and Regenerative Medicine, Department of General, Trauma, and Reconstruction Surgery, Ludwig-Maximilians University, Nussbaumstr 20, Munich, D-80336, Germany

    Attila Aszódi Ph.D.

Authors
  1. Attila Aszódi Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Attila Aszódi Ph.D. .

Editor information

Editors and Affiliations

  1. Orthopäd.KlinikUniversitätsklinikum.Rege, Orthopäd.KlinikfürdieUniversität.Regen., Regensburg, Germany

    Susanne Grässel

  2. Dept.ofGen.,Trauma&ReconstructionSurgery, Ludwig-Maximilians-University, Munich, Germany

    Attila Aszódi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Aszódi, A. (2016). The Cartilaginous Growth Plate. In: Grässel, S., Aszódi, A. (eds) Cartilage. Springer, Cham. https://doi.org/10.1007/978-3-319-29568-8_4

Download citation

Publish with us

Policies and ethics

Search

Navigation