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Original Article | Open Access

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate

Takeshi Oichi1,2,3( ), Joe Kodama1, Kimberly Wilson1, Hongying Tian1, Yuka Imamura Kawasawa4, Yu Usami5, Yasushi Oshima2, Taku Saito2, Sakae Tanaka2, Masahiro Iwamoto1, Satoru Otsuru1, Motomi Enomoto-Iwamoto1 ( )
Department of Orthopedics, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 1138655, Japan
Department of Orthopedics, Teikyo University School of Medicine, Tokyo 1738608, Japan
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Department of Oral Pathology, Osaka University Graduate School of Dentistry, Suita, Osaka 5650871, Japan
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Abstract

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate, where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Although nutritional status is a known regulator of long bone growth, it is largely unknown whether and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis in Axin2CreERT2 mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone and that exogenous IGF-1 restored the phosphorylated Akt level and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study of Axin2CreERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of chondroprogenitor cells.

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Bone Research
Volume 11,
December 2023
Article number: 20
DOI: 10.1038/s41413-023-00258-9
Cite this article:
Oichi T, Kodama J, Wilson K, et al. Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate. Bone Research, 2023, 11: 20. https://doi.org/10.1038/s41413-023-00258-9

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Received: 03 April 2022
Revised: 03 March 2023
Accepted: 09 March 2023
Published: 21 April 2023
© The Author(s) 2023

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