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

by Hallett, Shawn A , Nagata, Mizuki , Hirai, Takao , Matsushita, Yuki , Kronenberg, Henry M , Mizuhashi, Koji , Ono, Noriaki , Sakagami, Naoko , Zhou, Annabelle , Ono, Wanida , Tokavanich, Nicha

in Analysis / Animals / Antibiotics / bone / cartilage / Cell cycle / Cell Differentiation / Cell division / chondrocyte / Chondrocytes / Chondrocytes - cytology / Chondrocytes - metabolism / Developmental Biology / Doxycycline / Growth / Growth plate / Growth Plate - cytology / Growth Plate - metabolism / Histones / Mice / Parathyroid / Parathyroid hormone / Parathyroid hormone-related protein / Parathyroid Hormone-Related Protein - metabolism / Retention / skeletal stem cells / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Tetracycline / Tetracyclines / Wnt protein / wnt signaling / Wnt Signaling Pathway - physiology / β-Catenin

2021

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

by Hallett, Shawn A , Nagata, Mizuki , Hirai, Takao , Matsushita, Yuki , Kronenberg, Henry M , Mizuhashi, Koji , Ono, Noriaki , Sakagami, Naoko , Zhou, Annabelle , Ono, Wanida , Tokavanich, Nicha

2021

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

by Hallett, Shawn A , Nagata, Mizuki , Hirai, Takao , Matsushita, Yuki , Kronenberg, Henry M , Mizuhashi, Koji , Ono, Noriaki , Sakagami, Naoko , Zhou, Annabelle , Ono, Wanida , Tokavanich, Nicha

2021

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Journal Article

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

Hallett, Shawn A,

Nagata, Mizuki,

Hirai, Takao,

Matsushita, Yuki,

Kronenberg, Henry M,

Mizuhashi, Koji,

Ono, Noriaki,

Sakagami, Naoko,

Zhou, Annabelle,

Ono, Wanida,

Tokavanich, Nicha

2021

Overview

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.

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Publisher

eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

Subject

/ Animals

/ bone

/ Cell Differentiation