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

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 labelled “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.