ESPE Yearbook of Paediatric Endocrinology

In Brief: The authors use cell-tracing of Axin2-positive chondroprogenitor cells in the resting zone during and after food restriction to demonstrate that nutrient availability influences the balance between accumulation and differentiation of resting zone chondrocytes and that this is influenced by Igf-1.

Commentary: Catch-up growth is the rapid growth that occurs after growth-inhibiting conditions have been cured or removed. The molecular mechanism for catch-up growth has not been fully elucidated. According to the growth plate senescence model, growth-inhibiting conditions slow growth plate senescence. When the growth-inhibiting condition is removed, the growth plates are less senescent and therefore grow faster than normal for age, leading to catch-up growth¹.

These authors studied growth plate chondrocyte cell dynamics using an Axin2-Cre^ERT and different reporter strains to label and trace resting zone chondrocytes during and after food-restriction. Their findings confirm previous data that food-restriction delays the rate of senescent decline, growth plate height and the number of resting zone chondrocytes². Using cell-tracing techniques, they specifically showed that resting zone chondrocyte proliferation was maintained during food-restriction, but the transition from resting to proliferative chondrocytes was dramatically decreased, resulting in accumulation of resting zone chondrocytes. When food restriction was stopped, the accumulated resting zone chondrocytes were committed to the proliferative pool and contributed to catch-up growth.

This finding suggests that growth plates retain growth potential during growth-inhibiting conditions by maintain resting zone chondrocyte proliferation and simultaneously blocking their commitment to the proliferative pool, thus resulting in accumulation of resting zone chondrocytes. In addition, they show that the block in differentiation of resting to proliferative chondrocytes that occurs with food restriction can be overcome by treatment with exogenous IGF1, suggesting that IGF1 is required for differentiation of resting to proliferative chondrocytes and thus that decreased IGF1 may be the nutritional cue that the growth plate uses to conserve resting zone chondrocytes and thereby growth potential during food restriction.

References: 1. Gafni RI, Weise M, Robrecht DT, Meyers JL, Barnes KM, De-Levi S, Baron J. Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res. 2001 Nov;50(5):618–23. doi: 10.1203/00006450-200111000-00014. PMID: 11641457. 2. Shtaif B, Bar-Maisels M, Gabet Y, Hiram-Bab S, Yackobovitch-Gavan M, Phillip M, Gat-Yablonski G. Cartilage-specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency. Bone. 2020 Sep;138:115468. doi: 10.1016/j.bone.2020.115468. Epub 2020 Jun 5. PMID: 32512163.