Autophagy tunes chondrocyte differentiation and joint developmental precision in zebrafish

Abstract

Cartilage is a crucial component of the developing and functioning skeleton. It establishes a template for bone formation and comprises the articular cartilage for smooth joint movement. It is formed by dedicated matrix-secreting cells (chondrocytes) whose development and survival are negatively affected by disorders of crucial homeostatic and metabolic pathways, and by impaired ER and/or mitochondrial stress responses. As these processes are directly influenced by macroautophagy/autophagy, dysregulation of autophagy control in chondrocytes and their progenitors can contribute to human skeletal disorders, notably osteoarthritis (OA). To understand more about the contributions of autophagy during chondrogenesis, we characterized jaw joint development in a new zebrafish atg13 knockout line with reduced autophagic flux. In this model, embryonic lethality associated with restricted mouth opening range and premature chondrocyte hypertrophy are observed. Our data suggest that autophagy is required for timely chondrocyte maturation and extracellular matrix deposition, findings that highlight the importance of autophagy during normal joint formation.