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Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment.

eLife | 2021

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/β-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.

Pubmed ID: 34309509 RIS Download

Associated grants

  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE029181
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE026666
  • Agency: NIDCR NIH HHS, United States
    Id: F30 DE030675
  • Agency: NIDCR NIH HHS, United States
    Id: T32 DE007057
  • Agency: NIDDK NIH HHS, United States
    Id: P01 DK011794
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE030630

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