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Review
. 2019 Nov 29;20(23):6009.
doi: 10.3390/ijms20236009.

Growth Plate Chondrocytes: Skeletal Development, Growth and Beyond

Shawn A Hallett  1 , Wanida Ono  1 , Noriaki Ono  1
Affiliations
Review

Growth Plate Chondrocytes: Skeletal Development, Growth and Beyond

Shawn A Hallett et al. Int J Mol Sci. .

Abstract

Growth plate chondrocytes play central roles in the proper development and growth of endochondral bones. Particularly, a population of chondrocytes in the resting zone expressing parathyroid hormone-related protein (PTHrP) is now recognized as skeletal stem cells, defined by their ability to undergo self-renewal and clonally give rise to columnar chondrocytes in the postnatal growth plate. These chondrocytes also possess the ability to differentiate into a multitude of cell types including osteoblasts and bone marrow stromal cells during skeletal development. Using single-cell transcriptomic approaches and in vivo lineage tracing technology, it is now possible to further elucidate their molecular properties and cellular fate changes. By discovering the fundamental molecular characteristics of these cells, it may be possible to harness their functional characteristics for skeletal growth and regeneration. Here, we discuss our current understanding of the molecular signatures defining growth plate chondrocytes.

Keywords: chondrocyte; endochondral ossification; growth plate; hedgehog; osteoblast; parathyroid hormone-related protein; regeneration; skeleton.

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Conflict of interest statement

The authors declare no conflict of interest. Authors declare that there are no competing financial and/or non-financial interests regarding the publication of this paper. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Molecular characteristics of growth plate chondrocytes and their differentiation trajectories. The initial development of the secondary ossification center stimulates the formation of a PTHrP-labeled skeletal stem in the resting zone niche. This population contributes to the formation of proliferating and hypertrophic chondrocytes in addition to marking Col1a1+ osteoblasts in the primary spongiosa and Cxcl12+ bone marrow stromal cells in the marrow cavity over time. Moreover, the secondary ossification center promotes the establishment of a stem cell niche in the postnatal epiphyseal plate that is maintained by mTORC1 activity. Importantly, a paradigm has established that hypertrophic chondrocytes have the ability to ‘transdifferentiate’ into osteoblasts and further into more mature osteocytes over time, suggesting that this cell type, while terminally differentiated, does not always undergo apoptosis.
See this image and copyright information in PMC

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