Yap/Taz Orchestrates Chondrocyte Differentiation Fate in Fibrocartilage Development.

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)-CreERT2;Yapfl/fl;Tazfl/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.