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

eLife

Naoko Sakagami¹  Noriaki Ono²  Henry M Kronenberg³  Nicha Tokavanich⁴  Shawn A Hallett⁴  Takao Hirai⁴  Yuki Matsushita⁴  Mizuki Nagata⁴  Annabelle Zhou⁴  Koji Mizuhashi⁴  Wanida Ono⁴ 

[1] University of Texas Health Science Center at Houston School of Dentistry, Houston, United States;Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States;Ishikawa Prefectural Nursing University, Ishikawa, Japan;University of Michigan School of Dentistry, Ann Arbor, United States;

关键词: bone;    growth plate;    chondrocyte;    cartilage;    skeletal stem cells;    wnt signaling;   

DOI  :  10.7554/eLife.64513

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown