Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate.
Takeshi OichiJoe KodamaKimberly WilsonHongying TianYuka Imamura KawasawaYu UsamiYasushi OshimaTaku SaitoSakae TanakaMasahiro IwamotoSatoru OtsuruMasahiro IwamotoPublished in: Bone research (2023)
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 Axin2Cre ERT2 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 Axin2Cre ERT2 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.
Keyphrases
- induced apoptosis
- randomized controlled trial
- heart rate variability
- bone mineral density
- heart rate
- signaling pathway
- clinical trial
- transcription factor
- adipose tissue
- metabolic syndrome
- skeletal muscle
- cell cycle arrest
- postmenopausal women
- insulin resistance
- cell death
- high resolution
- young adults
- cross sectional