Research AppraisalSystematic Review

Quiescence in the resting zone of the growth plate: a systematic review

Stem cells (Dayton, Ohio)Avijgan, Mahtab, Nazaraliyev, Amal, Blomgren, Klas et al.25 Apr 2026DOI

Clinical Snapshot

45CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationResting zone chondrocytes in postnatal growth plates (primarily mouse models, some human studies)
I — InterventionStudies investigating cellular quiescence characteristics
C — ComparatorQuiescent cell populations in other well-studied tissues
O — OutcomesFeatures of cellular quiescence, molecular characterization, functional properties, cell division parameters

Bottom Line

This systematic review reveals significant knowledge gaps in our understanding of cellular quiescence in growth plate resting zone chondrocytes. While these cells have been labeled 'quiescent' for decades, the authors found that compared to well-studied quiescent cell populations in other tissues, resting zone chondrocytes lack proper molecular and functional characterization. The review identifies inconsistencies in how quiescence is defined and measured across studies, with most research focusing only on cell division parameters rather than comprehensive quiescence features. This work highlights the need for standardized approaches to studying growth plate stem cells and better integration of findings across studies. While not immediately clinically applicable, this research foundation is essential for understanding skeletal growth disorders and developing future therapeutic interventions for conditions affecting childhood growth and development.

Evidence: Moderate

Key Findings

  • Effect Size: Not applicable - qualitative systematic review

  • Primary Outcome: Features of cellular quiescence in resting zone chondrocytes remain poorly reported and underexplored compared to other tissues

  • Nnt Or Sensitivity: Not applicable - basic science review identifying research gaps

Clinical Application

Research findings may inform future therapeutic approaches for growth plate disorders but current clinical utility is minimal Relevant to paediatric orthopaedic research in Australian institutions; may inform TGA considerations for future growth-modulating therapies Limited direct clinical application - primarily relevant to researchers studying skeletal development and growth disorders

Abstract

Postnatal skeletal growth in childhood and adolescence depends on cartilage organs called (epiphyseal) growth plates. Studies in the last decade have identified populations of skeletal stem cells within mouse growth plates' resting zones. While cellular quiescence is vital for the maintenance of many tissue-resident stem cell populations, the resting zone chondrocytes have been labeled "quiescent" for decades. However, the features of cellular quiescence that have been reported in the postnatal resting zone, how they were defined or experimentally assessed, and knowledge gaps relative to other quiescent cell types, remain to be well described. To address this, we conducted a systematic review, using the PRISMA guidelines, to identify studies of resting zone chondrocytes including the prefix "quiescen*." Definitions, keywords, chronological data and experimental findings were extracted. Our analysis demonstrated that, compared to those in other well-studied tissues, features of cellular quiescence in RZ chondrocytes remain poorly reported and underexplored, with limited molecular and functional characterization. Furthermore, while most identified studies reported changes in cell division parameters, integration between cues controlling resting zone cell quiescence is incomplete and heterogeneity among the various sub-populations of RZ cells/potential quiescent states is yet to be fully determined. This review identifies consensuses and knowledge gaps between studies and between quiescent RZ cells and those in other tissues and can act to enhance consistency and comparability in future studies of "quiescence" in the RZ chondrocytes.

References

  1. 1.Avijgan, M., Nazaraliyev, A., Blomgren, K., Gomez-Cabrero, D., & Newton, P. T. (2026). Quiescence in the resting zone of the growth plate: a systematic review. Stem Cells, 41795828. https://doi.org/10.3389/fcell.2021.745069
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