Nutritional-induced longitudinal catch-up growth: A focus on the growth plate, growth-related genes, autophagy, mTOR, and microRNAs

The association between nutrition and linear growth in children is well accepted: the growth of the human skeleton requires an adequate supply of many different nutritional factors and a close relationship exists between mechanisms regulating weight and those regulating linear growth. Children with malnutrition have significantly lower body weight and height than healthy subjects, as well as reduced levels of serum leptin, insulin, and insulin-like growth factor-I. Catch-up (CU) growth is a phase of accelerated growth following correction of a temporary growth-retarding endocrinological, nutritional, medical, or emotional disorder, which allowed children to resume their pre-illness growth curve. However, the mechanism that underlies the body's "sensing" and "correction" of the growth delay as well as the exact mechanism whereby nutrition modulates cellular activity during bone elongation are still unclear. Several hormones, especially GH/IGF-I, leptin, and insulin, together with other as yet unidentified factors, affect local pathways that coordinate and couple chondrocyte proliferation and differentiation at the epiphyseal growth plate (EGP). Here we describe the effects of nutritional restriction and refeeding on the EGP, with a focus on growth-related genes. We also suggest the involvement of novel regulatory mechanisms in growth regulation including autophagy, mTOR, and microRNAs. A normal child is challenged with numerous episodes of growth-retarding causes (teeth eruption, minor infections, etc.), which are corrected without any long-standing effect. However, small alterations in the efficiency of the mechanism of the CU growth may lead eventually to significant differences in height. By understanding the mechanism of CU growth we may be able to design a better therapeutic regimen for children with growth disorders.