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.
Highlights
Growth and development of the axial and appendicular skeletons is a complex and multifactorial process tightly regulated by numerous signaling pathways
Most bones in the vertebrate skeleton are formed through endochondral ossification, in which an initial cartilage template is systematically replaced by bones [1]
These lineage-tracing, functional conditional knockout assays and skeletal regeneration studies demonstrate that parathyroid hormone-related protein (PTHrP)+ resting chondrocytes are a dedicated source of columnar chondrocytes in the growth plate by providing a forward PTHrP-mediated signal to transit-amplifying progeny in a non-cell autonomous manner, and that they are a fundamental driver for the explosive skeletal growth and bone elongation that occurs in mammals
Summary
Growth and development of the axial and appendicular skeletons is a complex and multifactorial process tightly regulated by numerous signaling pathways. Chondrocytes, which are derived from undifferentiated mesenchymal cells in condensations, serve to both drive the growth of the skeletal elements and to form a scaffold for the subsequent mineralization by osteoblasts [1]. Do chondrocytes provide the fundamental basis for proper skeletal development, their functions extend to support bone remodeling and regeneration during fracture healing. Recent applications of in vivo lineage-tracing approaches, single cell transcriptomics and various other omic technologies are beginning to open the avenue for elucidating the molecular properties of growth plate chondrocytes [2,3,4]. We will describe the fundamental properties and molecular regulators of growth plate chondrocytes and their roles in endochondral bone formation
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