ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 5.14 | DOI: 10.1530/ey.16.5.14

Department of Physiology and Pharmacology and Department of Women’s and Children’s Health, Karolinska Institutet and University Hospital, Stockholm, Sweden


Abstract: Nature. 2019 Mar;567(7747):234–238.

In brief: In this article, the authors present evidence that the murine epiphyseal growth plate develops a postnatal stem cell niche with monoclonal properties, that are able to self-renew. They thereby challenge the concept of a continous depletion of progenitor cells as a limiting factor for bone growth.

Comment: Linear growth depends on a constant generation of chondrocytes at the growth plates. Whereas the process of chondrocyte differentiation and endochondral ossification has been investigated in numerous studies, the precise origin of progenitor cells in the growth plate is not entirely understood. These authors aimed to determine the origin of growth plate chondrocytes and to question the concept of gradually exhausted stem-like chondroprogenitors with limited proliferative potential (1,2).

Using an elegant murine Confetti-reporter system, the authors confirmed that the stem-cell pool in the growth plate’s reserve zone was slowly depleted in fetal and neonatal mice. In contrast, the authors observed a sudden acquisition of stem cell renewal properties, leading to a coexistence of a multiclonal fetal and a monoclonal postnatal stem cell niche (Interactive model: http://chaginlab.com/sim) suggesting a switch in clonality associated with altered transcriptional activity. Interestingly, the onset of asymmetric stem-cell division was closely associated with the formation of the secondary centre of ossification (SOC), and inhibition of SOC maturation delayed development of monoclonality. Furthermore, the authors show evidence that the mTOR pathway has a central role in the regulation of the mode of clonality.

The hereby described mechanism of cell renewal in the growth plate resembles other tissues in need of continuous self renewal such as hair follicles or bone marrow. While the influence of the mTOR pathway in the regulation of clonality raises hopes for therapeutic options, a plurality of regulating pathways might be involved and remains to be investigated. Nevertheless, the discovery of this novel cellular niche opens doors to novel treatment strategies targeting the regenerative potential of growth plate chondrocytes in conditions such as skeletal dysplasias and osteoarthritis.

References: 1. Abad, V. et al. The Role of the Resting Zone in Growth Plate Chondrogenesis. Endocrinology 143, 1851–1857 (2002).

2. Hunziker, E. B. Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc. Res. Tech. 28, 505–519 (1994).

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