Yap/Taz Orchestrates Chondrocyte Differentiation Fate in Fibrocartilage Development

ABSTRACT The condyle is a key growth center of the mandible, covered by a layer of fibrocartilage. Through endochondral ossification, condylar cartilage drives mandibular elongation and height increase. However, the precise regulatory mechanism underlying this process remains unclear. In this study, we employed Aggrecan(Acan)‐Cre ERT2 ; Yap fl/fl ; Taz fl/fl mice to investigate the consequences of Yap/Taz deletion on chondrocyte differentiation and endochondral ossification during postnatal fibrocartilage development. Histological analysis revealed that the loss of Yap/Taz reduced the proportions of the superficial and proliferative zones but increased that of the hypertrophic layer. Micro‐CT analysis further showed that condylar height and subchondral bone formation were significantly decreased. Col X+ hypertrophic chondrocytes exhibited a stacked arrangement, yet failed to support endochondral ossification. Mechanistically, deletion of Yap/Taz likely suppresses Runx2 expression, thereby impairing the transdifferentiation potential of hypertrophic chondrocytes into osteoblasts. Collectively, these findings demonstrate that Yap/Taz inhibits chondrocyte maturation during chondrocyte differentiation while promoting chondrocyte transdifferentiation into osteoblasts at the subsequent endochondral ossification stage.