The Epiphyseal Growth Plate: The Engine That Drives Bone Elongation

  • Vickram Srinivas
  • Irving M. Shapiro


The goal of this chapter is to analyze the functional and molecular significance of the growth cartilage and to consider how this tissue, as a functional unit, promotes regulated bone growth. The epiphyseal growth plate comprises a thin film of transient cartilage that is most often located between the diaphysis and the secondary center of ossification. It contains just one cell type, chondrocytes; these cells undergo a complex differentiation process and secrete an abundant extracellular matrix. In this review, attention is directed at considering the unique structure of the growth plate itself and the associated bone, while considerable emphasis is placed on assessing the life history and function of the resident cells. Initially, chondrocytes within the growth plate undergo several rounds of proliferation and secrete a complex extracellular matrix that contains structural proteins, proteoglycans, and bioactive growth factors; when the replicative phase has ceased, chondrocytes increase their volume and undergo terminal differentiation. During this period, they continue to synthesize a unique extracellular matrix, undergo a shape change, bud-off matrix vesicles, and generate foci of mineral which eventually coalesce with other mineral deposits to form calcified cartilage. In this latter phase of their life history, the post-mitotic hypertrophic chondrocytes express an autophagic phenotype. Subsequently, these terminally differentiated chondrocytes are deleted from the plate by induction of the apoptotic process. The mineralized septa are then used as sites for deposition of bone mineral by osteoblasts, which then form many of the trabeculae of the underlying metaphyseal bone. In the review, considerable emphasis is placed on the mechanism by which the hypertrophic cell generates the space for new bone formation. Finally, following a discussion of the cellular and molecular characteristics of the growth plate, especially the mode of survival of cells in their hypoxic microenvironment, the mechanism by which growth factors regulate proliferation and hypertrophy is discussed.


Growth Plate Bone Growth Hypertrophic Chondrocytes Matrix Vesicle Autophagic Flux 
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.



Adenosine monophosphate kinase


B cell leukemia protein 2


Bone morphogenetic protein


BCL2/adenovirus E1B 19 kDa interacting protein 3




Calcium ion


Cartilage oligomeric protein


Extracellular signal-regulated kinase 1/2


Fibroblast growth factor


Fibroblast growth factor receptor


Histone deacetylase


Hypoxia-inducible factor


Indian hedgehog


Microtubule-associated light chain protein-3


Mitogen-activated protein kinase


Matrix metalloproteinase


Nitric oxide


Prolyl hydroxylase


Phosphate ion


Protein kinase C


Parathyroid hormone-related protein


Reactive oxygen species


Signal transducers and activators of transcription proteins


Transforming growth factor


Tissue inhibitor of matrix metalloproteinase


Vascular endothelial growth factor



The authors acknowledge the contract grant sponsor National Institutes of Health DE 015694 and DE 016383 (to VS) and DE 010875 and DE 013319 (to IMS).


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryJefferson Medical CollegePhiladelphiaUSA

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