First Author | Hallett SA | Year | 2021 |
Journal | Elife | Volume | 10 |
PubMed ID | 34309509 | Mgi Jnum | J:320594 |
Mgi Id | MGI:6816828 | Doi | 10.7554/eLife.64513 |
Citation | Hallett SA, et al. (2021) Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment. Elife 10:e64513 |
abstractText | Chondrocytes in the resting zone of the postnatal growth plate are characterized by slow cell cycle progression, and encompass a population of parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to the formation of columnar chondrocytes. However, how these chondrocytes are maintained in the resting zone remains undefined. We undertook a genetic pulse-chase approach to isolate slow cycling, label-retaining chondrocytes (LRCs) using a chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression of histone 2B-linked GFP. Comparative RNA-seq analysis identified significant enrichment of inhibitors and activators for Wnt signaling in LRCs and non-LRCs, respectively. Activation of Wnt/beta-catenin signaling in PTHrP(+) resting chondrocytes using Pthlh-creER and Apc-floxed allele impaired their ability to form columnar chondrocytes. Therefore, slow-cycling chondrocytes are maintained in a Wnt-inhibitory environment within the resting zone, unraveling a novel mechanism regulating maintenance and differentiation of PTHrP(+) skeletal stem cells of the postnatal growth plate. |