Apolipoprotein E is a marker of all chondrocytes in the growth plate resting zone

Joe Kodama ¹, Takeshi Oichi ¹, Kevin J Wilkinson ¹

⁰Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Bone Research +

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March 2, 2025

View abstract on PubMed

Summary

Apolipoprotein E (ApoE) is identified as a novel pan-resting chondrocyte (RC) marker in mammalian growth plates. This discovery aids in precisely identifying RCs, crucial for understanding bone growth and stem cell regulation.

Area Of Science

Skeletal Biology
Developmental Biology
Cell Biology

Background

The resting zone (RZ) of mammalian growth plates is vital for bone elongation, acting as a control tower and stem cell reservoir.
Current markers for resting chondrocytes (RCs) are incomplete, leading to heterogeneity and imprecise identification of RCs.
Histological criteria for RZ identification are ambiguous, causing inconsistencies in research.

Purpose Of The Study

To identify a comprehensive and precise marker for resting chondrocytes (RCs) in mammalian growth plates.
To resolve the heterogeneity observed within the RC population.
To establish a reliable method for defining the RZ.

Main Methods

Single-cell RNA sequencing (scRNAseq) of growth plate chondrocytes.
Validation of candidate markers using fluorescence in situ hybridization (FISH).
Generation and analysis of Apoe-mCherry knock-in mice to track ApoE-expressing cells.

Main Results

Apolipoprotein E (ApoE) was identified as a highly expressed gene in the RC cluster via scRNAseq.
FISH confirmed exclusive ApoE localization to the RZ in mouse growth plates.
ApoE-expressing RCs (marked by mCherry in knock-in mice) exhibited slow cycling in vivo and stem cell properties in vitro.
APOE expression was also detected in human growth plate RCs.

Conclusions

Apolipoprotein E (ApoE) serves as a novel pan-RC marker, applicable to both mouse and human growth plates.
This marker enables precise identification and characterization of RCs, advancing the study of bone growth.
The findings contribute to a better understanding of chondrocyte turnover and stem cell regulation in the growth plate.