Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea.

Aleksandra Marconi,J Andrew Gillis,Amy Hancock-Ronemus

doi:10.7554/elife.53414

Abstract

Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.

Highlights

Hyaline cartilage is a skeletal tissue that consists of a single cell type embedded within a homogeneous, collagenous extracellular matrix
We have shown that embryonic development of cartilage in the skate closely mirrors development of mammalian cartilage, but that unique features of the adult skate skeleton – including the presence of chondroprogenitors in the perichondrium and a network of cartilage canals – facilitates the continued growth of cartilage throughout life
Pre-skeletal mesenchyme aggregates to form a condensation at the site of skeletogenesis, and cells within this condensation undergo progressive differentiation, starting from the centre, into chondrocytes and eventually enlarged, hypertrophic chondrocytes (Hall, 2005; Karsenty et al, 2009; Long and Ornitz, 2013)

Summary

Introduction

Hyaline cartilage is a skeletal tissue that consists of a single cell type (the chondrocyte) embedded within a homogeneous, collagenous extracellular matrix (reviewed in Gillis, 2018). Chondrichthyans (cartilaginous fishes – sharks, skates, rays and holocephalans), on the other hand, possess an endoskeleton that is composed largely of hyaline cartilage, and that remains cartilaginous throughout life. Though chondrichthyans reinforce their endoskeleton with a superficial layer of calcified cartilage (in the form of small mineralized plates called ‘tesserae’ – Dean and Summers, 2006), the core of their endoskeletal elements persists as hyaline cartilage and does not undergo endochondral ossification.

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