Abstract
Bones elongate and children grow tall through the activities of a millimeter thin layer of cells wedged between the epiphyseal head and the diaphyseal shaft of the long bones. The form, function, and regulation of the activities of cells in this thin, transient, cartilaginous plate have fascinated scientists for a long time, and this growth plate is the focus of the studies reviewed in this chapter. A priori, it is important to acknowledge that apart from long bone, epiphyseal plate activity provides the mechanism of growth of almost all the osseous tissues of the human body. Moreover, other bone-related activities such as fracture repair share common pathways with those of chondrocytes located within the growth cartilage. Hence, an understanding of endochondral growth is relevant to bone elongation and repair, as well as systems that are central to cartilage formation, maturation and turnover.
Keywords
- Vascular Endothelial Growth Factor
- Growth Plate
- Hypoxia Inducible Factor
- Connective Tissue Growth Factor
- Hypertrophic Chondrocytes
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This work was supported by NIH grants DE 010875 (IMS) and DE 013319 (I.M.S.), and DE05262 (HCA).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
The complete PG works of Oliver Wendell Holmes, Sr. by Oliver Wendell Holmes, Sr. (The Physician and Poet) (World eBook Library PGCC Collection) (http://www.WorldLibrary.net).
- 2.
Lectures on the Comparative Anatomy and Physiology of the Vertebrate Animals: Delivered at the Royal College of Surgeons of England, in 1844, published by Longman, Brown, Green, and Longmans, 1846.
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 143:1851-1857
Agrawal A, Gajghate S, Smith H, Anderson DG, Albert TJ, Shapiro IM, Risbud MV (2008) Cited2 modulates hypoxia-inducible factor-dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc. Arthritis Rheum 58:3798-3808
Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B (2004) Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18:1072-1087
Ali SY, Sajdera SW, Anderson HC (1970) Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage. Proc Natl Acad Sci U S A 67:1513-1520
Alvarez J, Sohn P, Zeng X, Doetschman T, Robbins DJ, Serra R (2002) TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129:1913-1924
Anderson HC (1969) Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol 41:59-72
Anderson HC (1978) Introduction to the second conference on matrix vesicle calcification, Metab Bone Dis Relat Res 1 83-87
Anderson HC (1983) Calcific diseases. A concept. Arch Pathol Lab Med 107:341-348
Anderson HC (1985) Normal biological mineralization. Role of cells, membranes and matrix vesicles. In: Rubin RP, Weiss GF, Putney JW Jr (eds) Calcium in biological systems. Pienum, New York, p 600
Anderson HC, Garimella R, Tague SE (2005) The role of matrix vesicles in growth plate development and biomineralization. Front Biosci 10:822-837
Anderson HC, Hodges PT, Aguilera XM, Missana L, Moylan PE (2000) Bone morphogenetic protein (BMP) localization in developing human and rat growth plate, metaphysis, epiphysis, and articular cartilage. J Histochem Cytochem 48:1493-1502
Anderson HC, Hsu HH, Morris DC, Fedde KN, Whyte MP (1997) Matrix vesicles in osteomalacic hypophosphatasia bone contain apatite-like mineral crystals. Am J Pathol 151:1555-1561
Anderson HC, Reynolds JJ (1973) Pyrophosphate stimulation of calcium uptake into cultured embryonic bones. Fine structure of matrix vesicles and their role in calcification. Dev Biol 34:211-227
Anderson HC, Sipe JB, Hessle L, Dhanyamraju R, Atti E, Camacho NP, Millan JL (2004) Impaired calcification around matrix vesicles of growth plate and bone in alkaline phosphatase-deficient mice. Am J Pathol 164:841-847
Andrade AC, Nilsson O, Barnes KM, Baron J (2007) Wnt gene expression in the post-natal growth plate: regulation with chondrocyte differentiation. Bone 40:1361-1369
Balemans W, Van Hul W (2002) Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev Biol 250:231-250
Baron J, Klein KO, Colli MJ, Yanovski JA, Novosad JA, Bacher JD, Cutler GB Jr (1994) Catch-up growth after glucocorticoid excess: a mechanism intrinsic to the growth plate. Endocrinology 135:1367-1371
Baron J, Klein KO, Yanovski JA, Novosad JA, Bacher JD, Bolander ME, Cutler GB Jr (1994) Induction of growth plate cartilage ossification by basic fibroblast growth factor. Endocrinology 135:2790-2793
Barreto C, Albrecht RM, Bjorling DE, Horner JR, Wilsman NJ (1993) Evidence of the growth plate and the growth of long bones in juvenile dinosaurs. Science 262:2020-2023
Berndt T, Kumar R (2007) Phosphatonins and the regulation of phosphate homeostasis. Annu Rev Physiol 69:341-359
Blodgett FM, Burgin L, Iezzoni D, Gribetz D, Talbot NB (1956) Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children. N Engl J Med 254:636-641
Bohensky J, Shapiro IM, Leshinsky S, Terkhorn SP, Adams CS, Srinivas V (2007) HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic pathway. Autophagy 3:207-214
Boskey AL, Moore DJ, Amling M, Canalis E, Delany AM (2003) Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls. J Bone Miner Res 18:1005-1011
Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG Jr (2004) Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18: 2893-2904
Cardo-Vila M, Arap W, Pasqualini R (2003) Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V. Mol Cell 11:1151-1162
Cecil RNA, Anderson HC (1978) Freeze-fracture studies of matrix vesicle calcification in epiphyseal growth plate. Metab Bone Dis Relat Res 1:89-97
Chen CC, Boskey AL, Rosenberg LC (1984) The inhibitory effect of cartilage proteoglycans on hydroxyapatite growth. Calcif Tissue Int 36:285-290
Chen H, Shi H (2008) A reducing environment stabilizes HIF-2alpha in SH-SY5Y cells under hypoxic conditions. FEBS Lett 582:3899-3902
Chun JS, Oh H, Yang S, Park M (2008) Wnt signaling in cartilage development and degeneration. BMB Rep 41:485-494
Coffin JD, Florkiewicz RZ, Neumann J, Mort-Hopkins T, Dorn GW II, Lightfoot P, German R, Howles PN, Kier A, O’Toole BA et al (1995) Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Mol Biol Cell 6:1861-1873
D’Angelo M, Billings PC, Pacifici M, Leboy PS, Kirsch T (2001) Authentic matrix vesicles contain active metalloproteases (MMP). A role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-beta. J Biol Chem 276:11347-11353
Dai J, Rabie AB (2007) VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res 86:937-950
Davidson D, Blanc A, Filion D, Wang H, Plut P, Pfeffer G, Buschmann MD, Henderson JE (2005) Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem 280:20509-20515
De Luca F, Barnes KM, Uyeda JA, De-Levi S, Abad V, Palese T, Mericq V, Baron J (2001) Regulation of growth plate chondrogenesis by bone morphogenetic protein-2. Endocrinology 142:430-436
Dickson KM, Bergeron JJ, Philip A, O’Connor-McCourt M, Warshawsky H (2001) Localization of specific binding sites for 125I-TGF-beta1 to fenestrated endothelium in bone and anastomosing capillary networks in enamel organ suggests a role for TGF-beta1 in angiogenesis. Calcif Tissue Int 68:304-315
Ducy P, Geoffroy V, Karsenty G (1996) Study of osteoblast-specific expression of one mouse osteocalcin gene: characterization of the factor binding to OSE2. Connect Tissue Res 35:7-14
Enomoto-Iwamoto M, Kitagaki J, Koyama E, Tamamura Y, Wu C, Kanatani N, Koike T, Okada H, Komori T, Yoneda T, Church V, Francis-West PH, Kurisu K, Nohno T, Pacifici M, Iwamoto M (2002) The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev Biol 251:142-156
Farnum CE, Wilsman NJ (1989) Cellular turnover at the chondro-osseous junction of growth plate cartilage: analysis by serial sections at the light microscopical level. J Orthop Res 7:654-666
Farquharson C, Loveridge N (1990) Cell proliferation within the growth plate of long bones assessed by bromodeoxyuridine uptake and its relationship to glucose 6-phosphate dehydrogenase activity. Bone Miner 10:121-130
Felisbino SL, Carvalho HF (1999) The epiphyseal cartilage and growth of long bones in Rana catesbeiana. Tissue Cell 31:301-307
Fleisch H, Russell RG, Straumann F (1966) Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 212:901-903
Garcia-Ramirez M, Toran N, Andaluz P, Carrascosa A, Audi L (2000) Vascular endothelial growth factor is expressed in human fetal growth cartilage. J Bone Miner Res 15:534-540
Garimella R, Bi X, Camacho N, Sipe JB, Anderson HC (2004) Primary culture of rat growth plate chondrocytes: an in vitro model of growth plate histotype, matrix vesicle biogenesis and mineralization. Bone 34:961-970
Gay CV, Leach RM (1985) Tritiated thymidine uptake in chondrocytes of chickens afflicted with tibial dyschondroplasia. Avian Dis 29:1224-1229
Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623-628
Gordeladze JO, Reseland JE (2003) A unified model for the action of leptin on bone turnover. J Cell Biochem 88:706-712
Gordon MD, Nusse R (2006) Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 281:22429-22433
Haines RW (1975) The histology of epiphyseal union in mammals. J Anat 120:1-25
Hasky-Negev M, Simsa S, Tong A, Genina O, Monsonego Ornan E (2008) Expression of matrix metalloproteinases during vascularization and ossification of normal and impaired avian growth plate. J Anim Sci 86:1306-1315
Horner A, Bishop NJ, Bord S, Beeton C, Kelsall AW, Coleman N, Compston JE (1999) Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage. J Anat 194(pt 4):519-524
Horton WA, Hall JG, Hecht JT (2007) Achondroplasia. Lancet 370:162-172
Howell DS, Pita JC, Marquez JF, Madruga JE (1968) Partition of calcium, phosphate, and protein in the fluid phase aspirated at calcifying sites in epiphyseal cartilage. J Clin Invest 47:1121-1132
Hoyer-Hansen M, Jaattela M (2007) AMP-activated protein kinase: a universal regulator of autophagy? Autophagy 3:381-383
Huang H, He X (2008) Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20:119-125
Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49-60
Irie A, Habuchi H, Kimata K, Sanai Y (2003) Heparan sulfate is required for bone morphogenetic protein-7 signaling. Biochem Biophys Res Commun 308:858-865
Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM (2003) Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130:2779-2791
Jones RK, Searle RF, Stewart JA, Turner S, Bulmer JN (1998) Apoptosis, bcl-2 expression, and proliferative activity in human endometrial stroma and endometrial granulated lymphocytes. Biol Reprod 58:995-1002
Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15-25
Karaplis AC, He B, Nguyen MT, Young ID, Semeraro D, Ozawa H, Amizuka N (1998) Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia. Endocrinology 139:5255-5258
Karperien M, Lanser P, de Laat SW, Boonstra J, Defize LH (1996) Parathyroid hormone related peptide mRNA expression during murine postimplantation development: evidence for involvement in multiple differentiation processes. Int J Dev Biol 40:599-608
Kember NF (1972) Comparative patterns of cell division in epiphyseal cartilage plates in the rat. J Anat 111:137-142
Kerr BA, Otani T, Koyama E, Freeman TA, Enomoto-Iwamoto M (2008) Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes. Exp Cell Res 314:1301-1312
Kirsch T (2005) Annexins - their role in cartilage mineralization. Front Biosci 10:576-581
Kitsoulis P, Galani V, Stefanaki K, Paraskevas G, Karatzias G, Agnantis NJ, Bai M (2008) Osteochondromas: review of the clinical, radiological and pathological features. In Vivo 22:633-646
Klionsky DJ, Cregg JM, Dunn WA Jr, Emr SD, Sakai Y, Sandoval IV, Sibirny A, Subramani S, Thumm M, Veenhuis M, Ohsumi Y (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5:539-545
Kobayashi T, Soegiarto DW, Yang Y, Lanske B, Schipani E, McMahon AP, Kronenberg HM (2005) Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest 115:1734-1742
Krejci P, Krakow D, Mekikian PB, Wilcox WR (2007) Fibroblast growth factors 1, 2, 17, and 19 are the predominant FGF ligands expressed in human fetal growth plate cartilage. Pediatr Res 61:267-272
Kronenberg HM (2006) PTHrP and skeletal development. Ann N Y Acad Sci 1068:1-13
Kronenberg HM (2007) The role of the perichondrium in fetal bone development. Ann N Y Acad Sci 1116:59-64
Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT (2000) The Wnt/Ca2 + pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 16:279-283
Landis WJ, Arsenault AL (1989) Vesicle- and collagen-mediated calcification in the turkey leg tendon. Connect Tissue Res 22:35-42; discussion 53-61
Lazarus JE, Hegde A, Andrade AC, Nilsson O, Baron J (2007) Fibroblast growth factor expression in the postnatal growth plate. Bone 40:577-586
Lee ER, Lamplugh L, Shepard NL, Mort JS (1995) The septoclast, a cathepsin B-rich cell involved in the resorption of growth plate cartilage. J Histochem Cytochem 43:525-536
Lee YJ, Park JH, Ju SK, You KH, Ko JS, Kim HM (2002) Leptin receptor isoform expression in rat osteoblasts and their functional analysis. FEBS Lett 528:43-47
Levine B, Sinha S, Kroemer G (2008) Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4:600-606
Liu Z, Lavine KJ, Hung IH, Ornitz DM (2007) FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Dev Biol 302:80-91
Lum JJ, DeBerardinis RJ, Thompson CB (2005) Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 6:439-448
Magne D, Bluteau G, Faucheux C, Palmer G, Vignes-Colombeix C, Pilet P, Rouillon T, Caverzasio J, Weiss P, Daculsi G, Guicheux J (2003) Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: possible implication of apoptosis in the regulation of endochondral ossification. J Bone Miner Res 18:1430-1442
Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3-15
Mak KK, Chen MH, Day TF, Chuang PT, Yang Y (2006) Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development 133:3695-3707
Mancilla EE, De Luca F, Uyeda JA, Czerwiec FS, Baron J (1998) Effects of fibroblast growth factor-2 on longitudinal bone growth. Endocrinology 139:2900-2904
Maniatopoulos C, Sodek J, Melcher AH (1988) Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res 254:317-330
Mansfield K, Pucci B, Adams CS, Shapiro IM (2003) Induction of apoptosis in skeletal tissues: phosphate-mediated chick chondrocyte apoptosis is calcium dependent. Calcif Tissue Int 73:161-172
Mansfield K, Teixeira CC, Adams CS, Shapiro IM (2001) Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone 28:1-8
Matsuzawa T, Anderson HC (1971) Phosphatases of epiphyseal cartilage studied by electron microscopic cytochemical methods. J Histochem Cytochem 19:801-808
Milgram JW (1983) The origins of osteochondromas and enchondromas. A histopathologic study. Clin Orthop Relat Res 264-284
Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A (2002) Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell 3:439-449
Minina E, Schneider S, Rosowski M, Lauster R, Vortkamp A (2005) Expression of Fgf and Tgfbeta signaling related genes during embryonic endochondral ossification. Gene Expr Patterns 6:102-109
Minina E, Wenzel HM, Kreschel C, Karp S, Gaffield W, McMahon AP, Vortkamp A (2001) BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development 128:4523-4534
Montessuit C, Caverzasio J, Bonjour JP (1991) Characterization of a Pi transport system in cartilage matrix vesicles. Potential role in the calcification process. J Biol Chem 266:17791-17797
Nagayama M, Iwamoto M, Hargett A, Kamiya N, Tamamura Y, Young B, Morrison T, Takeuchi H, Pacifici M, Enomoto-Iwamoto M, Koyama E (2008) Wnt/beta-catenin signaling regulates cranial base development and growth. J Dent Res 87:244-249
Nahar NN, Missana LR, Garimella R, Tague SE, Anderson HC (2008) Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins. J Bone Miner Metab 26:514-519
Nilsson O, Parker EA, Hegde A, Chau M, Barnes KM, Baron J (2007) Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol 193:75-84
Niswander L, Martin GR (1993) FGF-4 and BMP-2 have opposite effects on limb growth. Nature 361:68-71
Nusse R (1996) Patching up Hedgehog. Nature 384: 119-120
Oshima Y, Akiyama T, Hikita A, Iwasawa M, Nagase Y, Nakamura M, Wakeyama H, Kawamura N, Ikeda T, Chung UI, Hennighausen L, Kawaguchi H, Nakamura K, Tanaka S (2008) Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis. J Biol Chem 283:26499-26508
Pan Y, Mansfield KD, Bertozzi CC, Rudenko V, Chan DA, Giaccia AJ, Simon MC (2007) Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 27:912-925
Parfitt AM (2002) Misconceptions (1): epiphyseal fusion causes cessation of growth. Bone 30:337-339
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927-939
Peress NS, Anderson HC, Sajdera SW (1974) The lipids of matrix vesicles from bovine fetal epiphyseal cartilage. Calcif Tissue Res 14:275-281
Pettifor JM (2008) What’s new in hypophosphataemic rickets? Eur J Pediatr 167:493-499
Provot S, Schipani E (2007) Fetal growth plate: a developmental model of cellular adaptation to hypoxia. Ann N Y Acad Sci 1117:26-39
Pucci B, Adams CS, Fertala J, Snyder BC, Mansfield KD, Tafani M, Freeman T, Shapiro IM (2007) Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation. J Cell Physiol 210: 609-615
Rajpurohit R, Koch CJ, Tao Z, Teixeira CM, Shapiro IM (1996) Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism. J Cell Physiol 168:424-432
Rajpurohit R, Mansfield K, Ohyama K, Ewert D, Shapiro IM (1999) Chondrocyte death is linked to development of a mitochondrial membrane permeability transition in the growth plate. J Cell Physiol 179:287-296
Roach HI, Aigner T, Kouri JB (2004) Chondroptosis: a variant of apoptotic cell death in chondrocytes? Apoptosis 9:265-277
Rozenblut B, Ogielska M (2005) Development and growth of long bones in European water frogs (Amphibia: Anura: Ranidae), with remarks on age determination. J Morphol 265:304-317
Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9:267-285
Sabbagh Y, Carpenter TO, Demay MB (2005) Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci U S A 102: 9637-9642
Schinke T, Amendt C, Trindl A, Poschke O, Muller-Esterl W, Jahnen-Dechent W (1996) The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 271:20789-20796
Schipani E, Kruse K, Juppner H (1995) A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268:98-100
Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15:2865-2876
Schlaepfer DD, Jones J, Haigler HT (1992) Inhibition of protein kinase C by annexin V. Biochemistry 31:1886-1891
Shapiro IM, Adams CS, Freeman T, Srinivas V (2005) Fate of the hypertrophic chondrocyte: microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate. Birth Defects Res C Embryo Today 75:330-339
Shapiro IM, Mansfield KD, Evans SM, Lord EM, Koch CJ (1997) Chondrocytes in the endochondral growth cartilage are not hypoxic. Am J Physiol 272:C1134-C1143
Shapiro IM, Srinivas V (2007) Metabolic consideration of epiphyseal growth: survival responses in a taxing environment. Bone 40:561-567
Shukunami C, Oshima Y, Hiraki Y (2005) Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis inhibitors found in hypovascular connective tissues. Biochem Biophys Res Commun 333:299-307
Simon MC (2006) Coming up for air: HIF-1 and mitochondrial oxygen consumption. Cell Metab 3:150-151
Smink JJ, Buchholz IM, Hamers N, van Tilburg CM, Christis C, Sakkers RJ, de Meer K, van Buul-Offers SC, Koedam JA (2003) Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis. Osteoarthritis Cartilage 11:864-871
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 189:88-92
Takada T, Katagiri T, Ifuku M, Morimura N, Kobayashi M, Hasegawa K, Ogamo A, Kamijo R (2003) Sulfated polysaccharides enhance the biological activities of bone morphogenetic proteins. J Biol Chem 278:43229-43235
Takahara M, Naruse T, Takagi M, Orui H, Ogino T (2004) Matrix metalloproteinase-9 expression, tartrate-resistant acid phosphatase activity, and DNA fragmentation in vascular and cellular invasion into cartilage preceding primary endochondral ossification in long bones. J Orthop Res 22:1050-1057
Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, Yamada Y, Costantini F, Wakisaka S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 280:19185-19195
Tanaka N, Ohno S, Honda K, Tanimoto K, Doi T, Ohno-Nakahara M, Tafolla E, Kapila S, Tanne K (2005) Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel. J Dent Res 84:64-68
Tanner JM, Davies PS (1985) Clinical longitudinal standards for height and height velocity for North American children. J Pediatr 107:317-329
Teixeira CC, Ischiropoulos H, Leboy PS, Adams SL, Shapiro IM (2005) Nitric oxide-nitric oxide synthase regulates key maturational events during chondrocyte terminal differentiation. Bone 37: 37-45
Teixeira CC, Rajpurohit R, Mansfield K, Nemelivsky YV, Shapiro IM (2003) Maturation-dependent thiol loss increases chondrocyte susceptibility to apoptosis. J Bone Miner Res 18:662-668
Teixeira CC, Shapiro IM, Hatori M, Rajpurohit R, Koch C (1996) Retinoic acid modulation of glutathione and cysteine metabolism in chondrocytes. Biochem J 314(pt 1):21-26
Terkhorn SP, Bohensky J, Shapiro IM, Koyama E, Srinivas V (2007) Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: relationship between maturation and apoptotic sensitivity. J Cell Physiol 210:257-265
Thomas T, Martin A (2005) Bone metabolism and energy balance: role for leptin. Joint Bone Spine 72:471-473
Tiet TD, Alman BA (2003) Developmental pathways in musculoskeletal neoplasia: involvement of the Indian hedgehog-parathyroid hormone-related protein pathway. Pediatr Res 53:539-543
van der Eerden BC, Karperien M, Wit JM (2003) Systemic and local regulation of the growth plate. Endocr Rev 24:782-801
Vanky P, Brockstedt U, Hjerpe A, Wikstrom B (1998) Kinetic studies on epiphyseal growth cartilage in the normal mouse. Bone 22:331-339
Veeman MT, Axelrod JD, Moon RTA (2003) second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell 5:367-377
Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613-622
Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93:411-422
Wang W, Kirsch T (2006) Annexin V/beta5 integrin interactions regulate apoptosis of growth plate chondrocytes. J Biol Chem 281:30848-30856
Wang Y, Toury R, Hauchecorne M, Balmain N (1997) Expression of Bcl-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats. Histochem Cell Biol 108:45-55
Watanabe H, Bohensky J, Freeman T, Srinivas V, Shapiro IM (2008) Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy. J Cell Physiol 216:419-425
Wilsman NJ, Farnum CE, Leiferman EM, Fry M, Barreto C (1996) Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J Orthop Res 14:927-936
Wu Q, Zhang Y, Chen Q (2001) Indian hedgehog is an essential component of mechanotransduction complex to stimulate chondrocyte proliferation. J Biol Chem 276:35290-35296
Wyllie AH, Golstein P (2001) More than one way to go. Proc Natl Acad Sci U S A 98:11-13
Yoon BS, Lyons KM (2004) Multiple functions of BMPs in chondrogenesis. J Cell Biochem 93:93-103
Zhong M, Wike LJ, Ryaby JT, Carney DH, Boyan BD, Schwartz Z (2008) Thrombin peptide TP508 prevents nitric oxide mediated apoptosis in chondrocytes in the endochondral developmental pathway. Biochim Biophys Acta 1783:12-22
zur Nieden NI, Kempka G, Rancourt DE, Ahr HJ (2005) Induction of chondro-, osteo- and adipogenesis in embryonic stem cells by bone morphogenetic protein-2: effect of cofactors on differentiating lineages. BMC Dev Biol 5:1
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag London
About this chapter
Cite this chapter
Anderson, H.C., Shapiro, I.M. (2010). The Epiphyseal Growth Plate. In: Bronner, F., Farach-Carson, M., Roach, H. (eds) Bone and Development. Topics in Bone Biology, vol 6. Springer, London. https://doi.org/10.1007/978-1-84882-822-3_3
Download citation
DOI: https://doi.org/10.1007/978-1-84882-822-3_3
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-84882-821-6
Online ISBN: 978-1-84882-822-3
eBook Packages: MedicineMedicine (R0)