Cadherin 19 deficiency inhibits osteogenic differentiation and bone formation by regulating PI3K/AKT signaling pathway

• CDH19 deficiency impairs osteoblast proliferation and differentiation, leading to reduced bone mass and microstructural deterioration. • CDH19 knockout mice exhibit decreased bone density, trabecular number, and bone volume fraction, confirming its essential role in bone formation. • Mechanistically, CDH19 deletion suppresses the PI3K/AKT signaling pathway, as revealed by RNA-seq and Western blot analyses. • Activation of PI3K/AKT with agonist 740Y-P partially rescues the osteogenic inhibition caused by CDH19 loss, suggesting a potential therapeutic strategy.