Dataset Information

Possible Contribution of Wnt-Responsive Chondroprogenitors to the Postnatal Murine Growth Plate.

ABSTRACT: Active cell proliferation and turnover in the growth plate is essential for embryonic and postnatal bone growth. We performed a lineage tracing of Wnt/?-catenin signaling responsive cells (Wnt-responsive cells) using Axin2CreERT2 ;Rosa26ZsGreen mice and found a novel cell population that resides in the outermost layer of the growth plate facing the Ranvier's groove (RG; the perichondrium adjacent to growth plate). These Wnt-responsive cells rapidly expanded and contributed to formation of the outer growth plate from the neonatal to the growing stage but stopped expanding at the young adult stage when bone longitudinal growth ceases. In addition, a second Wnt-responsive sporadic cell population was localized within the resting zone of the central part of the growth plate during the postnatal growth phase. While it induced ectopic chondrogenesis in the RG, ablation of ?-catenin in the Wnt-responsive cells strongly inhibited expansion of their descendants toward the growth plate. These findings indicate that the Wnt-responsive cell population in the outermost layer of the growth plate is a unique cell source of chondroprogenitors involving lateral growth of the growth plate and suggest that Wnt/?-catenin signaling regulates function of skeletal progenitors in a site- and stage-specific manner. © 2019 American Society for Bone and Mineral Research.

SUBMITTER: Usami Y

PROVIDER: S-EPMC6536347 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Possible Contribution of Wnt-Responsive Chondroprogenitors to the Postnatal Murine Growth Plate.

Usami Yu Y Gunawardena Aruni T AT Francois Noelle B NB Otsuru Satoru S Takano Hajime H Hirose Katsutoshi K Matsuoka Masatake M Suzuki Akiko A Huang Jiahui J Qin Ling L Iwamoto Masahiro M Yang Wentian W Toyosawa Satoru S Enomoto-Iwamoto Motomi M

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20190128 5

Active cell proliferation and turnover in the growth plate is essential for embryonic and postnatal bone growth. We performed a lineage tracing of Wnt/β-catenin signaling responsive cells (Wnt-responsive cells) using Axin2<sup>CreERT2</sup> ;Rosa26ZsGreen mice and found a novel cell population that resides in the outermost layer of the growth plate facing the Ranvier's groove (RG; the perichondrium adjacent to growth plate). These Wnt-responsive cells rapidly expanded and contributed to formatio ...[more]

PMID: 30602070

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Project description:Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers-the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may contribute to the spatial differentiation of chondrocytes in the postnatal endochondral skeleton.

Dataset Information

Possible Contribution of Wnt-Responsive Chondroprogenitors to the Postnatal Murine Growth Plate.

Publications

Possible Contribution of Wnt-Responsive Chondroprogenitors to the Postnatal Murine Growth Plate.

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