Physiology and pathophysiology of the growth plate

Abstract

Longitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate. Through a sequential process of cell proliferation, extracellular matrix synthesis, cellular hypertrophy, matrix mineralization, vascular invasion, and eventually apoptosis, the cartilage model is continually replaced by bone as length increases. The regulation of longitudinal growth at the growth plate occurs generally through the intimate interaction of circulating systemic hormones and locally produced peptide growth factors, the net result of which is to trigger changes in gene expression by growth plate chondrocytes. This review highlights recent advances in genetics and cell biology that are illuminating the important regulatory mechanisms governing the structure and biology of the growth plate, and provides selected examples of how studies of human mutations have yielded a wealth of new knowledge regarding the normal biology and pathophysiology of growth plate cartilage.

Sorting of growth plate chondrocytes allows the isolation and characterization of cells of a defined differentiation status

“…Chondroblasts within the resting/proliferative zone are committed to enter a continuous differentiation and maturation process that terminates in hypertrophic cartilage, which becomes calcified, resorbed by osteoclasts, and then replaced by primary bone trabeculae in a process termed endochondral ossification. (1) Defects in growth plate development and its homeostasis caused by abnormal proliferation and maturation of chondrocytes may result in skeletal chondrodysplasias, dwarfism, and skeletal malformations. (2) Considerable insight into the pathogenesis of human chondrodysplasias has been gained from studies of mouse models, (3,4) which also provide important information on the cell biology of normal cartilage development and maturation.…”

Three‐dimensional in situ zonal morphology of viable growth plate chondrocytes: A confocal microscopy study

“…In the reserve zone, cells are randomly dispersed through the matrix alone or in couples. 2,4,5 In the proliferative zone, chondrocytes have a flattened appearance and are organized in columns. 5 Chondrocytes located at epiphyseal end of the proliferative zone divide rapidly while chondrocytes located at metaphyseal end of the proliferative columns start to increase in size towards the hypertrophic zone.…”

“…2,4,5 In the proliferative zone, chondrocytes have a flattened appearance and are organized in columns. 5 Chondrocytes located at epiphyseal end of the proliferative zone divide rapidly while chondrocytes located at metaphyseal end of the proliferative columns start to increase in size towards the hypertrophic zone. [6][7][8][9][10][11] In the hypertrophic zone, cell division stops and terminal differentiation associated with a large increase in cell volume begins.…”

“…[6][7][8][9][10][11] In the hypertrophic zone, cell division stops and terminal differentiation associated with a large increase in cell volume begins. 5 The mechanisms by which growth plate chondrocytes modulate longitudinal bone growth are still not well understood. Hypertrophy (changes in cell volume and height), proliferation of chondrocytes as well as matrix synthesis have been implicated as the most important factors in both normal and mechanically modulated growth of long bones.…”

Endochondral ossification of the mouse nasal septum

“…Endochondral ossification is the process of replacing cartilage matrix with bone matrix and occurs at growth plates and synchondroses (Ballock and O'Keefe, 2003). The growth plate comprises four discrete zones: a resting zone, in which cells are relatively quiescent; a proliferative zone, formed by short columns of dividing cells; a hypertrophic zone, in which chondrocytes swell, mineralize the surrounding matrix, and die by apoptosis; and an ossification zone, in which blood vessels invade, and osteoblasts deposit bone matrix onto the mineralized cartilage matrix [terminology from Hunziker et al (1987)].…”