Children grow taller because their bones grow longer.
This bone elongation occurs at the growth plate, a cartilaginous structure that is located near the ends of long bones, the short tubular bones of the hands and feet and the vertebrae. The growth plate is composed of three layers: the resting, proliferative and hypertrophic zones (Fig. 1).
The resting zone serves as a reservoir of progenitor chondrocytes (Abad et al, 2002). The proliferative zone, which contains chondrocytes arrayed in columns, is the site of rapid cell proliferation (Fig. 1) (2). At one edge of the proliferative zone, the cells stop dividing and become enlarged to form hypertrophic chondrocytes (Fig. 1). This cell proliferation and cell hypertrophy, combined with extracellular matrix secretion, result in chondrogenesis, that is, the production of more and more cartilage. In isolation, this chondrogenesis would cause the cartilaginous growth plate to become progressively wider with age. However, simultaneously, blood vessels, osteoclasts, and osteoblasts invade the hypertrophic zone and remodel the newly formed cartilage into bone. The net result is that new bone is formed at the bottom of the growth plate, causing the bones to grow longer and the child to grow taller.
Chondrogenesis in the growth plate is controlled by multiple interacting regulatory systems, involving endocrine, paracrine, extracellular matrix, and intracellular pathways.
The endocrine signals include growth hormone, insulin-like growth factor I, glucocorticoids, thyroid hormone, estrogens, and androgens. Many of these signals regulate growth plate function both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Paracrine signals that regulate chondrogenesis include FGFs, BMPs, IGFs, C-type natriuretic peptide, retinoids, WNTs, PTHrP/IHH.
Longitudinal bone growth slows with age and eventually ceases.
This growth deceleration appears to be due to a mechanism intrinsic to the growth plate which we have termed growth plate senesecence. We have found evidence that senescence occurs because growth plate chondrocytes have a finite proliferative capacity that is gradually exhausted causing growth to slow and finally stop (Nilsson et al, 2014).
Genetic disorders of the growth plate cause substantial morbidity. More than 1 in 5000 children suffer from genetic disorders of the growth plate, which often cause severe short stature and bone deformity. These disorders include skeletal dysplasias, syndromic short stature, and severe, isolated short stature. Our research exploring the fundamental molecular and cellular mechanisms governing longitudinal bone growth may help elucidate the pathophysiology of growth failure and thus lead to improved diagnosis and treatment. We seek to understand skeletal growth not only for the direct clinical applications but also to uncover general principles of developmental biology. The cellular processes underlying bone growth, such as cell proliferation, terminal differentiation, angiogenesis, and cell migration, are also essential for development in other tissues.