ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Development 2017; 144:3533-3546

Endochondral ossification is the process by which the embryonic cartilaginous scaffold of most bones is gradually replaced by bone. During this process chondrocytes proliferate, undergo hypertrophy and maturation and form the growth plate, essential for bone growth. Postnatal bone growth is tightly regulated by both systemic and local factors, many of which not yet identified.

IGF2 has an established role in fetal development and growth; its expression has been found in several tissues during the early postnatal period [49] but that relevance is not fully elucidated. IGF2 is involved in the regulation of the musculoskeletal system and is an osteoblast survival factor influencing cell replication, collagen production and matrix apposition [50]. IGF2 is expressed in the growth plate and its mutations have been recently recognized as responsible for severe postnatal growth restriction in humans [51].

In this elegant study in a murine model, the authors demonstrate that IGF2 regulates chondrocyte development by modulating a) progression of chondrocytes from the proliferating to the hypertrophic phase; b) perichondrial cell proliferation and differentiation; c) chondrocyte glucose metabolism, keeping both anaerobic glycolysis and oxidative phosphorylation under control. In humans, a nonsense mutation (p.Ser64Ter) in IGF2 was identified in a family with some members who had severe prenatal and postnatal growth restriction [51]. The results of this experimental study provide evidence for a key role of IGF2 in cartilage growth thus explaining at least part of the phenotype observed in patients with IGF2 mutation.

49. DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991;64:849-59.

50. Livingstone C, Borai A. Insulin-like growth factor-II: its role in metabolic and endocrine disease. Clin Endocrinol. 2014;80:773-81.

51. Begemann M, Zirn B, Santen G, Wirthgen E, Soellner L, Buttel HM, et al. Paternally Inherited IGF2 Mutation and Growth Restriction. N Engl J Med. 2015;373:349-56.