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Growth and Development of Articular Cartilage

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Articular Cartilage of the Knee

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Abstract

Cartilage is a dynamic tissue with enhanced complexity attributed to the existence of numerous developmental phases and overlap in phenotypic gene expression with related cell types. This chapter reviews the recent advances in molecular biology that illuminate the factors that drive and control articular cartilage growth and development. The objective is to provide a better understanding of the key molecular and genetic participants during the growth and development of articular-epiphyseal cartilage (AEC) and the epiphyseal growth plate (GP).

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References

  1. Solursh M. Ectoderm as a determinant of early tissue pattern in the limb bud. Cell Differ. 1984;15:17–24.

    Article  CAS  PubMed  Google Scholar 

  2. Solursh M. Cartilage stem cells: regulation of differentiation. Connect Tissue Res. 1989;20:81–9.

    Article  CAS  PubMed  Google Scholar 

  3. Solursh M. Extracellular matrix and cell surface as determinants of connective tissue differentiation. Am J Med Genet. 1989;34:30–4.

    Google Scholar 

  4. Grafe I, Alexander S, Peterson JR, Snider TN, Levi B, Lee B, Mishina Y. TGF-β family signaling in mesenchymal differentiation. Cold Spring Harb Perspect Biol. 2018;10(5): pii a022202.

    Google Scholar 

  5. Decker RS. Articular cartilage and joint development from emb ryogenesis to adulthood. Semin Cell Dev Biol. 2017;62:50–6.

    Article  PubMed  Google Scholar 

  6. Li Y, Jin D, Xie W, Wen L, Chen W, Xu J, Ding J, Ren D. PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Curr Stem Cell Res Ther. 2018;13(3):185–92.

    Article  CAS  PubMed  Google Scholar 

  7. Visco DM, Van Sickle DC, Hill MA, Kincaid SA. The vascular supply of the chondro-epiphyses of the elbow joint in young swine. J Anat. 1989;163:215–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Clark JM. The structure of vascular channels in the subchondral plate. J Anat. 1990;171:105–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Green WT Jr, Martin GN, Eanes ED, Sokoloff L. Microradiographic study of the calcified layer of articular cartilage. Arch Pathol. 1970;90:151–8.

    CAS  PubMed  Google Scholar 

  10. Lane LB, Bullough PG. Age-related changes in the thickness of the calcified zone and the number of tidemarks in adult human articular cartilage. J Bone Joint Surg. 1980;62:372–5.

    Article  CAS  Google Scholar 

  11. Eyre DR, Dickson IR, Van Ness K. Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues. Biochem J. 1988;252:495–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pal S, Tang LH, Choi H, Habermann E, Rosenberg L, Roughley P, Poole AR. Structural changes during development in bovine fetal epiphyseal cartilage. Coll Relat Res. 1981;1:151–76.

    Article  CAS  PubMed  Google Scholar 

  13. Thonar EJ, Sweet MB. Maturation-related changes in proteoglycans of fetal articular cartilage. Arch Biochem Biophys. 1981;208:535–47.

    Article  CAS  PubMed  Google Scholar 

  14. Rux D, Decker RS, Koyama E, Pacifici M. Joints in the appendicular skeleton: developmental mechanisms and evolutionary influences. Curr Top Dev Biol. 2019;133:119–51.

    Google Scholar 

  15. Wong M, Carter DR. Mechanical stress and morphogenetic endochondral ossification of the sternum. J Bone Joint Surg Am. 1988;70:992–1000.

    Article  CAS  PubMed  Google Scholar 

  16. Takada N, Wada I, Sugimura I, Sakuma E, Maruyama H, Matsui N. A possible barrier function of the articular surface, Kaibogaku zasshi. J Anat. 1999;74:631–7.

    CAS  Google Scholar 

  17. Gannon AR, Nagel T, Bell AP, Avery NC, Kelly DJ. The changing role of the superficial region in determining the dynamic compressive properties of articular cartilage during postnatal development. Osteoarthritis Cartilage. 2015;23(6):975–84.

    Article  CAS  PubMed  Google Scholar 

  18. Kaviani R, Londono I, Parent S, Moldovan F, Villemure I. Changes in growth plate extracellular matrix composition and biomechanics following in vitro static versus dynamic mechanical modulation. J Musculoskelet Neuronal Interact. 2018;18(1):81–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Woods A, Wang G, Beier F. Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions. J Cell Physiol. 2007;213:1–8.

    Article  CAS  PubMed  Google Scholar 

  20. Lories RJ, Corr M, Lane NE. To Wnt or not to Wnt: the bone and joint health dilemma. Nat Rev Rheumatol. 2013;9:328–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Green JD, Tollemar V, Dougherty M, Yan Z, Yin L, Ye J, Collier Z, Mohammed MK, Haydon RC, Luu HH, Kang R, Lee MJ, Ho SH, He TC, Shi LL, Athiviraham A. Multifaceted signaling regulators of chondrogenesis: implications in cartilage regeneration and tissue engineering. Genes Dis. 2015;2:307–27.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jing J, Hinton RJ, Feng JQ. Bmpr1a signaling in cartilage development and endochondral bone formation. Vitam Horm. 2015;99:273–91.

    Article  CAS  PubMed  Google Scholar 

  23. Somoza RA, Welter JF, Correa D, Caplan AI. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng Part B Rev. 2014;20:596–608.

    Google Scholar 

  24. Lefebvre V, Dvir-Ginzberg M. SOX9 and the many facets of its regulation in the chondrocyte lineage. Connect Tissue Res. 2016;58(1):2–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Nilsson O, Marino R, De Luca F, Phillip M, Baron J. Endocrine regulation of the growth plate. Horm Res. 2005;64:157–65.

    CAS  PubMed  Google Scholar 

  26. Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. J Cell Biochem. 2006;97:33–44.

    Article  CAS  PubMed  Google Scholar 

  27. Thorogood PV, Hinchliffe JR. An analysis of the condensation process during chondrogenesis in the embryonic chick hind limb. J Embryol Exp Morphol. 1975;33:581–606.

    CAS  PubMed  Google Scholar 

  28. Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. 1999;22:85–9.

    Article  CAS  PubMed  Google Scholar 

  29. Gardner OF, Archer CW, Alini M, Stoddart MJ. Chondrogenesis of mesenchymal stem cells for cartilage tissue engineering. Histol Histopathol. 2013;28:23–42.

    CAS  PubMed  Google Scholar 

  30. Archer CW, Francis-West P. The chondrocyte. Int J Biochem Cell Biol. 2003;35:401–4.

    Article  CAS  PubMed  Google Scholar 

  31. Cole AG. A review of diversity in the evolution and development of cartilage: the search for the origin of the chondrocyte. Eur Cell Mater. 2011;21:122–9.

    Article  CAS  PubMed  Google Scholar 

  32. Olsen BR, Reginato AM, Wang W. Bone development. Annu Rev Cell Dev Biol. 2000;16:191–220.

    Article  CAS  PubMed  Google Scholar 

  33. Sandell LJ, Nalin AM, Reife RA. Alternative splice form of type II procollagen mRNA (IIA) is predominant in skeletal precursors and non-cartilaginous tissues during early mouse development. Dev Dyn. 1994;199:129–40.

    Google Scholar 

  34. Kosher RA. In: Hall BK, editor. The chondroblast and the chondrocyte. New York: Academic Press, Inc; 1983. p. 59–85.

    Google Scholar 

  35. Fell HB. The histogenesis of cartilage and bone in the long bones of the embryonic fowl. J Morphol. 1925;40:417–59.

    Article  Google Scholar 

  36. Hall BK, Miyake T. All for one and one for all: condensations and the initiation of skeletal development. Bioessays. 2000;22:138–47.

    Article  CAS  PubMed  Google Scholar 

  37. DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage. 2000;8:309–34.

    Google Scholar 

  38. Janners MY, Searls RL. Changes in rate of cellular proliferation during the differentiation of cartilage and muscle in the mesenchyme of the embryonic chick wing. Dev Biol. 1970;23:136–65.

    Article  CAS  PubMed  Google Scholar 

  39. Archer CW, Rooney P, Wolpert L. Cell shape and cartilage differentiation of early chick limb bud cells in culture. Cell Differ. 1982;11:245–51.

    Article  CAS  PubMed  Google Scholar 

  40. Ghosh S, Laha M, Mondal S, Sengupta S, Kaplan DL. In vitro model of mesenchymal condensation during chondrogenic development. Biomaterials. 2009;30:6530–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Erlebacher A, Filvaroff EH, Gitelman SE, Derynck R. Toward a molecular understanding of skeletal development. Cell. 1995;80:371–8.

    Article  CAS  PubMed  Google Scholar 

  42. Tchetina EV. Developmental mechanisms in articular cartilage degradation in osteoarthritis. Arthritis. 2011;2011:683970.

    Article  PubMed  Google Scholar 

  43. Chung UI. Essential role of hypertrophic chondrocytes in endochondral bone development. Endocr J. 2004;51:19–24.

    Article  PubMed  Google Scholar 

  44. Tickle C. Molecular basis of vertebrate limb patterning. Am J Med Genet. 2002;112:250–5.

    Article  PubMed  Google Scholar 

  45. Towers M, Tickle C. Generation of pattern and form in the developing limb. Int J Dev Biol. 2009;53:805–12.

    Article  PubMed  Google Scholar 

  46. Niswander L. Pattern formation: old models out on a limb. Nat Rev Genet. 2003;4:133–43.

    Article  CAS  PubMed  Google Scholar 

  47. Kosher RA, Savage MP, Walker KH. A gradation of hyaluronate accumulation along the proximodistal axis of the embryonic chick limb bud. J Embryol Exp Morphol. 1981;63:85–98.

    CAS  PubMed  Google Scholar 

  48. Toole BP, Okayama M, Orkin RW, Yoshimura M, Muto M, Kaji A. Developmental roles of hyaluronate and chondroitin sulfate proteoglycans. Soc Gen Physiol Ser. 1977;32:139–54.

    CAS  PubMed  Google Scholar 

  49. Toole BP, Gross J. The extracellular matrix of the regenerating newt limb: synthesis and removal of hyaluronate prior to differentiation. Dev Biol. 1971;25:57–77.

    Article  CAS  PubMed  Google Scholar 

  50. Delise AM, Tuan RS. Analysis of N-cadherin function in limb mesenchymal chondrogenesis in vitro. Dev Dyn. 2002;225:195–204.

    Google Scholar 

  51. Tuan RS. Cellular signaling in developmental chondrogenesis: N-cadherin, Wnts, and BMP-2. J Bone Joint Surg Am. 2003;85-A(Suppl 2):137–41.

    Article  Google Scholar 

  52. Dessau W, von der Mark H, von der Mark K, Fischer S. Changes in the patterns of collagens and fibronectin during limb-bud chondrogenesis. J Embryol Exp Morphol. 1980;57:51–60.

    CAS  PubMed  Google Scholar 

  53. Biddulph DM, Sawyer LM, Smales WP. Chondrogenesis of chick limb mesenchyme in vitro. Effects of prostaglandins on cyclic AMP. Exp Cell Res. 1984;153:270–4.

    Article  CAS  PubMed  Google Scholar 

  54. Ballard TA, Biddulph DM. The morphology and hormonal responsiveness of developing skeletal elements in chick limb buds. Am J Anat. 1984;169:221–36.

    Article  CAS  PubMed  Google Scholar 

  55. Kosher RA, Walker KH, Ledger PW. Temporal and spatial distribution of fibronectin during development of the embryonic chick limb bud. Cell Differ. 1982;11:217–28.

    Article  CAS  PubMed  Google Scholar 

  56. Stirpe NS, Goetinck PF. Gene regulation during cartilage differentiation: temporal and spatial expression of link protein and cartilage matrix protein in the developing limb. Development. 1989;107:23–33.

    CAS  PubMed  Google Scholar 

  57. Liu CF, Lefebvre V. The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis. Nucleic Acids Res. 2015;43:8183–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kosher RA, Kulyk WM, Gay SW. Collagen gene expression during limb cartilage differentiation. J Cell Biol. 1986;102:1151–6.

    Article  CAS  PubMed  Google Scholar 

  59. Kosher RA, Solursh M. Widespread distribution of type II collagen during embryonic chick development. Dev Biol. 1989;131:558–66.

    Article  CAS  PubMed  Google Scholar 

  60. Kravis D, Upholt WB. Quantitation of type II procollagen mRNA levels during chick limb cartilage differentiation. Dev Biol. 1985;108:164–72.

    Article  CAS  PubMed  Google Scholar 

  61. Nah HD, Rodgers BJ, Kulyk WM, Kream BE, Kosher RA, Upholt WB. In situ hybridization analysis of the expression of the type II collagen gene in the developing chicken limb bud. Coll Relat Res. 1988;8:277–94.

    Article  CAS  PubMed  Google Scholar 

  62. Swiderski RE, Solursh M. Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton. Dev Dyn. 1992;194:118–27.

    Google Scholar 

  63. Kulyk WM, Coelho CN, Kosher RA. Type IX collagen gene expression during limb cartilage differentiation. Matrix. 1991;11:282–8.

    Google Scholar 

  64. Swiderski RE, Solursh M. Differential co-expression of long and short form type IX collagen transcripts during avian limb chondrogenesis in ovo. Development. 1992;115:169–79.

    CAS  PubMed  Google Scholar 

  65. Barone LM, Owen TA, Tassinari MS, Bortell R, Stein GS, Lian JB. Developmental expression and hormonal regulation of the rat matrix Gla protein (MGP) gene in chondrogenesis and osteogenesis. J Cell Biochem. 1991;46:351–65.

    Article  CAS  PubMed  Google Scholar 

  66. Luo G, D'Souza R, Hogue D, Karsenty G. The matrix Gla protein gene is a marker of the chondrogenesis cell lineage during mouse development. J Bone Miner Res. 1995;10:325–34.

    Google Scholar 

  67. Hale JE, Fraser JD, Price PA. The identification of matrix Gla protein in cartilage. J Biol Chem. 1988;263:5820–4.

    CAS  PubMed  Google Scholar 

  68. Hascall VC, Oegema TR, Brown M, Caplan AI. Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro. J Biol Chem. 1976;251:3511–9.

    CAS  PubMed  Google Scholar 

  69. Palmoski MJ, Goetinck PF. Synthesis of proteochondroitin sulfate by normal, nanomelic, and 5-bromodeoxyuridine-treated chondrocytes in cell culture. Proc Natl Acad Sci U S A. 1972;69:3385–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mallein-Gerin F, Kosher RA, Upholt WB, Tanzer ML. Temporal and spatial analysis of cartilage proteoglycan core protein gene expression during limb development by in situ hybridization. Dev Biol. 1988;126:337–45.

    Article  CAS  PubMed  Google Scholar 

  71. Tsonis PA, Walker E. Cell populations synthesizing cartilage proteoglycan core protein in the early chick limb bud. Biochem Biophys Res Commun. 1991;174:688–95.

    Article  CAS  PubMed  Google Scholar 

  72. Topol L, Chen W, Song H, Day TF, Yang Y. Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus. J Biol Chem. 2009;284:3323–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lefebvre V, Smits P. Transcriptional control of chondrocyte fate and differentiation. Birth Defects Res C Embryo Today. 2005;75:200–12.

    Google Scholar 

  74. Adams SL, Cohen AJ, Lassova L. Integration of signaling pathways regulating chondrocyte differentiation during endochondral bone formation. J Cell Physiol. 2007;213:635–41.

    Article  CAS  PubMed  Google Scholar 

  75. Gamer LW, Pregizer S, Gamer J, Feigenson M, Ionescu A, et al. The role of Bmp2 in the maturation and maintenance of the murine knee joint. J Bone Miner Res. 2018;33(9):1708–17.

    Google Scholar 

  76. de Crombrugghe B, Lefebvre V, Nakashima K. Regulatory mechanisms in the pathways of cartilage and bone formation. Curr Opin Cell Biol. 2001;13:721–7.

    Article  PubMed  Google Scholar 

  77. Zelzer E, Olsen BR. The genetic basis for skeletal diseases. Nature. 2003;423:343–8.

    Article  CAS  PubMed  Google Scholar 

  78. Las Heras F, Pritzker KP, So A, Tsui HW, Chiu B, Inman RD, Tsui FW. Aberrant chondrocyte hypertrophy and activation of beta-catenin signaling precede joint ankylosis in ank/ank mice. J Rheumatol. 2012;39:583–93.

    Article  CAS  PubMed  Google Scholar 

  79. Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M. Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol. 2008;40:46–62.

    Article  CAS  PubMed  Google Scholar 

  80. Long F, Ornitz DM. Development of the endochondral skeleton. Cold Spring Harb Perspect Biol. 2013;5:a008334.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Catheline SE, Hoak D, Chang M, Ketz JP, Hilton MJ, et al. Chondrocyte-specific RUNX2 overexpression accelerates post-traumatic osteoarthritis progression in adult mice. J Bone Miner Res. 2019;34(9):1676–89.

    Google Scholar 

  82. Yoshida CA, Komori T. Role of Runx proteins in chondrogenesis. Crit Rev Eukaryot Gene Expr. 2005;15:243–54.

    Article  CAS  PubMed  Google Scholar 

  83. Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, Yamana K, Zanma A, Takada K, Ito Y, Komori T. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 2004;18:952–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Leboy P, Grasso-Knight G, D'Angelo M, Volk SW, Lian JV, Drissi H, Stein GS, Adams SL. Smad-Runx interactions during chondrocyte maturation. J Bone Joint Surg Am. 2001;83-A(Suppl 1):S15–22.

    Google Scholar 

  85. Iwai T, Murai J, Yoshikawa H, Tsumaki N. Smad7 Inhibits chondrocyte differentiation at multiple steps durin g endochondral bone formation and down-regulates p38 MAPK pathways. J Biol Chem. 2008;283:27154–64.

    Article  CAS  PubMed  Google Scholar 

  86. Ballock RT, Heydemann A, Wakefield LM, Flanders KC, Roberts AB, Sporn MB. TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases. Dev Biol. 1993;158:414–29.

    Article  CAS  PubMed  Google Scholar 

  87. Solomon LA, Berube NG, Beier F. Transcriptional regulators of chondrocyte hypertrophy. Birth Defects Res C Embryo Today. 2008;84:123–30.

    Google Scholar 

  88. Poole AR. An introduction to the pathophysiology of osteoarthritis. Front Biosci. 1999;4:D662–70.

    Google Scholar 

  89. Archer CW, Morrison H, Pitsillides AA. Cellular aspects of the development of diarthrodial joints and articular cartilage. J Anat. 1994;184(Pt 3):447–56.

    PubMed  PubMed Central  Google Scholar 

  90. Hayes AJ, MacPherson S, Morrison H, Dowthwaite G, Archer CW. The development of articular cartilage: evidence for an appositional growth mechanism. Anat Embryol. 2001;203:469–79.

    Article  CAS  Google Scholar 

  91. Babyn PS, Kim HK, Lemaire C, Gahunia HK, Cross A, DeNanassy J, Pritzker KP. High-resolution magnetic resonance imaging of normal porcine cartilaginous epiphyseal maturation. J Magn Reson Imaging JMRI. 1996;6:172–9.

    Article  CAS  PubMed  Google Scholar 

  92. Kim HK, Babyn PS, Harasiewicz KA, Gahunia HK, Pritzker KP, Foster FS. Imaging of immature articular cartilage using ultrasound backscatter microscopy at 50 MHz. J Orthop Res. 1995;13:963–70.

    Google Scholar 

  93. Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J. The role of the resting zone in growth plate chondrogenesis. Endocrinology. 2002;143:1851–7.

    Article  CAS  PubMed  Google Scholar 

  94. Farnum CE, Wilsman NJ. Morphologic stages of the terminal hypertrophic chondrocyte of growth plate cartilage. Anat Rec. 1987;219:221–32.

    Article  CAS  PubMed  Google Scholar 

  95. Emons J, Chagin AS, Savendahl L, Karperien M, Wit JM. Mechanisms of growth plate maturation and epiphyseal fusion. Horm Res Paediatr. 2011;75:383–91.

    Article  CAS  PubMed  Google Scholar 

  96. Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J. Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci U S A. 2001;98:6871–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gafni RI, Weise M, Robrecht DT, Meyers JL, Barnes KM, De-Levi S, Baron J. Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res. 2001;50:618–23.

    Article  CAS  PubMed  Google Scholar 

  98. Dailey L, Laplantine E, Priore R, Basilico C. A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation. J Cell Biol. 2003;161(6):1053–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Haines RW. The development of joints. J Anat. 1947;81:33–55.

    PubMed  PubMed Central  Google Scholar 

  100. Garciadiego-Cazares D, Rosales C, Katoh M, Chimal-Monroy J. Coordination of chondrocyte differentiation and joint formation by alpha5beta1 integrin in the developing appendicular skeleton. Development. 2004;131:4735–42.

    Article  CAS  PubMed  Google Scholar 

  101. Ploger F, Seemann P, Schmidt-von Kegler M, Lehmann K, Seidel J, Kjaer KW, Pohl J, Mundlos S. Brachydactyly type A2 associated with a defect in proGDF5 processing. Hum Mol Genet. 2008;17:1222–33.

    Article  PubMed  CAS  Google Scholar 

  102. Francis-West PH, Abdelfattah A, Chen P, Allen C, Parish J, Ladher R, Allen S, MacPherson S, Luyten FP, Archer CW. Mechanisms of GDF-5 action during skeletal development. Development. 1999;126:1305–15.

    CAS  PubMed  Google Scholar 

  103. Chijimatsu R, Saito T. Mechanisms of synovial joint and articular cartilage development. Cell Mol Life Sci. 2019;76(20):3939–52.

    Google Scholar 

  104. Moses HL, Serra R. Regulation of differentiation by TGF-beta. Curr Opin Genet Dev. 1996;6:581–6.

    Article  CAS  PubMed  Google Scholar 

  105. Serra R, Johnson M, Filvaroff EH, LaBorde J, Sheehan DM, Derynck R, Moses HL. Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol. 1997;139:541–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Brunet LJ, McMahon JA, McMahon AP, Harland RM. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 1998;280:1455–7.

    Google Scholar 

  107. Daans M, Lories RJ, Luyten FP. Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease. Arthritis Res Ther. 2008;10:R115.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Cheng A, Gustafson AR, Schaner Tooley CE, Zhang M. BMP-9 dependent pathways required for the chondrogenic differentiation of pluripotent stem cells. Differentiation. 2016;92(5):298–305.

    Article  CAS  PubMed  Google Scholar 

  109. Drissi H, Gibson JD, Guzzo RM, RH X. Derivation and chondrogenic commitment of human embryonic stem cell-derived mesenchymal progenitors. Methods Mol Biol. 2015;1340:65–78.

    Google Scholar 

  110. Ray A, Singh PN, Sohaskey ML, Harland RM, Bandyopadhyay A. Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation. Development. 2015;142:1169–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Retting KN, Song B, Yoon BS, Lyons KM. BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development. 2009;136:1093–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hoffmann A, Gross G. BMP signaling pathways in cartilage and bone formation. Crit Rev Eukaryot Gene Expr. 2001;11:23–45.

    Article  CAS  PubMed  Google Scholar 

  113. van der Eerden BC, Karperien M, Wit JM. Systemic and local regulation of the growth plate. Endocr Rev. 2003;24:782–801.

    Article  PubMed  CAS  Google Scholar 

  114. Barna M, Niswander L. Visualization of cartilage formation: insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes. Dev Cell. 2007;12:931–41.

    Article  CAS  PubMed  Google Scholar 

  115. Grimsrud CD, Romano PR, D'Souza M, Puzas JE, Reynolds PR, Rosier RN, O'Keefe RJ. BMP-6 is an autocrine stimulator of chondrocyte differentiation. J Bone Miner Res. 1999;14:475–82.

    Google Scholar 

  116. Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell. 2002;3:439–49.

    Article  CAS  PubMed  Google Scholar 

  117. Grimsrud CD, Romano PR, D’Souza M, Puzas JE, Schwarz EM, Reynolds PR, Roiser RN, O’Keefe RJ. BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog. J Orthop Res. 2001;19:18–25.

    Article  CAS  PubMed  Google Scholar 

  118. Yoon BS, Pogue R, Ovchinnikov DA, Yoshii I, Mishina Y, Behringer RR, Lyons KM. BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways. Development. 2006;133:4667–78.

    Article  CAS  PubMed  Google Scholar 

  119. Jung YK, Kim GW, Park HR, Lee EJ, Choi JY, Beier F, Han SW. Role of interleukin-10 in endochondral bone formation in mice: anabolic effect via the bone morphogenetic protein/Smad pathway. Arthritis Rheum. 2013;65:3153–64.

    Article  CAS  PubMed  Google Scholar 

  120. Malinauskas T, Jones EY. Extracellular modulators of Wnt signalling. Curr Opin Struct Biol. 2014;29:77–84.

    Article  CAS  PubMed  Google Scholar 

  121. Kikuchi A, Yamamoto H, Kishida S. Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal. 2007;19:659–71.

    Article  CAS  PubMed  Google Scholar 

  122. Cadigan KM, Liu YI. Wnt signaling: complexity at the surface. J Cell Sci. 2006;119:395–402.

    Article  CAS  PubMed  Google Scholar 

  123. Moon RT. Wnt/beta-catenin pathway. Sci STKE. 2005: 2005(271): cm1.

    Google Scholar 

  124. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387–98.

    Article  CAS  PubMed  Google Scholar 

  125. Chen Y, Alman BA. Wnt pathway, an essential role in bone regeneration. J Cell Biochem. 2009;106:353–62.

    Article  CAS  PubMed  Google Scholar 

  126. Ma B, Landman EB, Miclea RL, Wit JM, Robanus-Maandag EC, Post JN, Karperien M. WNT signaling and cartilage: of mice and men. Calcif Tissue Int. 2013;92:399–411.

    Article  CAS  PubMed  Google Scholar 

  127. Staines KA, Macrae VE, Farquharson C. Cartilage development and degeneration: a Wnt Wnt situation. Cell Biochem Funct. 2012;30:633–42.

    Article  CAS  PubMed  Google Scholar 

  128. Usami Y, Gunawardena AT, Iwamoto M, Enomoto-Iwamoto M. Wnt signaling in cartilage development and diseases: lessons from animal studies. Lab Invest. 2016;96:186–96.

    Google Scholar 

  129. Huang Y, Jiang L, Yang H, Wu L, Xu N, et al. Variations of Wnt/β-catenin pathway-related genes in susceptibility to knee osteoarthritis: a three-centre case-control study. J Cell Mol Med. 2019. doi: 10.1111/jcmm.14696. [Epub ahead of print]

    Google Scholar 

  130. 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. Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem. 2005;280:19185–95.

    Article  CAS  PubMed  Google Scholar 

  131. Yuan X, Liu H, Huang H, Liu H, Li L, Yang J, Shi W, Liu W, Wu L. The key role of canonical Wnt/beta-catenin signaling in cartilage chondrocytes. Curr Drug Targets. 2016;17:475–84.

    Article  CAS  PubMed  Google Scholar 

  132. Zhong N, Gersch RP, Hadjiargyrou M. Wnt signaling activation during bone regeneration and the role of Dishevelled in chondrocyte proliferation and differentiation. Bone. 2006;39:5–16.

    Article  CAS  PubMed  Google Scholar 

  133. Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8:727–38.

    Article  CAS  PubMed  Google Scholar 

  134. Dao DY, Yang X, Chen D, Zuscik M, O’Keefe RJ. Axin1 and Axin2 are regulated by TGF- and mediate cross-talk between TGF- and Wnt signaling pathways. Ann N Y Acad Sci. 2007;1116:82–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Church V, Nohno T, Linker C, Marcelle C, Francis-West P. Wnt regulation of chondrocyte differentiation. J Cell Sci. 2002;115:4809–18.

    Article  CAS  PubMed  Google Scholar 

  136. Gaur T, Rich L, Lengner CJ, Hussain S, Trevant B, Ayers D, Stein JL, Bodine PV, Komm BS, Stein GS, Lian JB. Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation. J Cell Physiol. 2006;208:87–96.

    Article  CAS  PubMed  Google Scholar 

  137. Bodine PV, Zhao W, Kharode YP, Bex FJ, Lambert AJ, Goad MB, Gaur T, Stein GS, Lian JB, Komm BS. The Wnt antagonist secreted frizzledrelated protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol. 2004;18:1222–37.

    Article  CAS  PubMed  Google Scholar 

  138. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008;4:550–6.

    Article  CAS  PubMed  Google Scholar 

  139. Wu Q, Zhu M, Rosier RN, Zuscik MJ, O’Keefe RJ, Chen D. Beta-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci. 2010;1192:344–50.

    Google Scholar 

  140. Kawaguchi H. Regulation of osteoarthritis development by Wnt-beta-catenin signaling through the endochondral ossification process. J Bone Miner Res. 2009;24:8–11.

    Google Scholar 

  141. Wang L, Shao YY, Ballock RT. Leptin synergizes with thyroid hormone signaling in promoting growth plate chondrocyte proliferation and terminal differentiation in vitro. Bone. 2011;48:1022–7.

    Article  CAS  PubMed  Google Scholar 

  142. Maeda Y, Nakamura E, Nguyen MT, Suva LJ, Swain FL, Razzaque MS, Mackem S, Lanske B. Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone. Proc Natl Acad Sci U S A. 2007;104:6382–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. van der Eerden BC, Karperien M, Gevers EF, Lowik CW, Wit JM. Expression of Indian hedgehog, parathyroid hormone-related protein, and their receptors in the postnatal growth plate of the rat: evidence for a locally acting growth restraining feedback loop after birth. J Bone Miner Res. 2000;15:1045–55.

    Google Scholar 

  144. Karp SJ, Schipani E, St-Jacques B, Hunzelman J, Kronenberg H, McMahon AP. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development. 2000;127:543–8.

    CAS  PubMed  Google Scholar 

  145. Kohn A, Rutkowski TP, Liu Z, Mirando AJ, Zuscik MJ, O'Keefe RJ, Hilton MJ. Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9. Bone Res. 2015;3:15021.

    Google Scholar 

  146. Estrada KD, Wang W, Retting KN, Chien CT, Elkhoury FF, Heuchel R, Lyons KM. Smad7 regulates terminal maturation of chondrocytes in the growth plate. Dev Biol. 2013;382:375–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Dong Y, Drissi H, Chen M, Chen D, Zuscik MJ, Schwarz EM, O'Keefe RJ. Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta. J Cell Biochem. 2005;95:1057–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cawston TE, Wilson AJ. Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract Res Clin Rheumatol. 2006;20:983–1002.

    Article  CAS  PubMed  Google Scholar 

  149. Inada M, Wang Y, Byrne MH, Rahman MU, Miyaura C, Lopez-Otin C, Krane SM. Critical roles for collagenase-3 (Mmp-13) in development of growth plate cartilage and in endochondral ossification. Proc Natl Acad Sci U S A. 2004;101:17192–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ortega N, Behonick DJ, Werb Z. Matrix remodeling during endochondral ossification. Trends Cell Biol. 2004;4:86–93.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Departamento de Anatomia Patologica, Clinica Las Condes, Santiago, Chile

    Facundo Las Heras MD, PhD

  2. Pathology Department, University of Chile, Santiago, Chile

    Facundo Las Heras MD, PhD

  3. Orthopaedic Science Consulting Services, Oakville, ON, Canada

    Harpal K. Gahunia MSc, PhD

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  1. Facundo Las Heras MD, PhD
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Correspondence to Facundo Las Heras MD, PhD .

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Editors and Affiliations

  1. Orthopaedic Science Consulting Services, Oakville, ON, Canada

    Harpal K. Gahunia

  2. Division of Orthopaedic Surgery, University of Toronto, Toronto, ON, Canada

    Allan E. Gross

  3. Department of Laboratory Medicine and Pathobiology, Department of Surgery, and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Kenneth P.H. Pritzker

  4. Saskatchewan Health Authority Department Head of Medical Imaging, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada

    Paul S. Babyn

  5. Division of Orthopaedic Surgery, University of Toronto, Toronto, ON, Canada

    Lucas Murnaghan

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Las Heras, F., Gahunia, H.K. (2020). Growth and Development of Articular Cartilage. In: Gahunia, H., Gross, A., Pritzker, K., Babyn, P., Murnaghan, L. (eds) Articular Cartilage of the Knee. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7587-7_2

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