ESPE Abstracts (2015) 84 S10.1

Molecular Mechanisms of Growth Plate Adaptation During Undernutrition

Francesco De Luca

St Christopher’s Hospital for Children, Philadelphia, Pennsylvania, USA

It is known that almost 180 million children in the world have stunted growth. Most of these children live in eastern and central Africa and in South-central Asia. Among multiple factors causing stunted growth in the developing world, malnutrition is the most important one. On the other hand, reduced caloric intake is also a cause of poor statural growth in developed countries.

Mammals, including humans, exposed to malnutrition experience poor bone growth through a number of adaptive mechanisms affecting endocrine factors as well as paracrine factors in the growth plate. For instance, malnutrition-related deficiencies of endocrine factors such as IGF1, insulin, and leptin lead to impaired statural growth. It has also been shown that microRNAs and enzymes like Sirtuin1 may be implicated in growth adaptation during malnutrition by regulating the activity of systemic and paracrine growth factors. Lastly, recent evidence indicates that the changes in expression of fibroblast growth factor 21 (FGF21) associated with caloric reduction can adversely affect growth plate chondrogenesis and bone growth both systemically and locally within the growth plate. Increased FGF21 action during chronic undernutrition causes GH resistance/IGF1 deficiency and, in turn, reduced growth plate function and bone growth.

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