Smad4 deficiency impairs chondrocyte hypertrophy via the Runx2 transcription factor in mouse skeletal development [RNA-seq]

Smad4 is a central mediator of canonical TGF/BMP signaling and plays important roles in mesenchymal cell aggregation, chondrocyte differentiation, osteoblast differentiation and maturation. However, the regulatory mechanism of Smad4 underlying chondrocyte hypertrophy during skeletal development is unknown. To elucidate the molecular mechanism by which Smad4 deficiency impairs chondrocyte hypertrophy, we performed high-throughput RNA-seq to identify target genes involved in Smad4-regulated chondrocyte hypertrophy. Our results suggest that Smad4 controls chondrocyte hypertrophy through regulating Runx2 expression during skeletal development. We performed high-throughput RNA-seq to examine genes with altered expression in Smad4-/- forelimbs at E11.5-E14.5.Smad4是经典TGF/BMP信号通路的核心介导因子，在间充质细胞聚集、软骨细胞分化、成骨细胞分化与成熟过程中发挥重要作用。然而，骨骼发育过程中Smad4调控软骨细胞肥大的分子机制尚未明确。为阐明Smad4缺失损害软骨细胞肥大的分子机制，我们通过高通量RNA测序（RNA-seq）筛选参与Smad4调控软骨细胞肥大的靶基因。研究结果表明，Smad4在骨骼发育过程中通过调控Runx2的表达来控制软骨细胞肥大。我们通过高通量RNA测序，检测了胚胎发育第11.5天至第14.5天的Smad4-/-小鼠前肢中表达异常的基因。