Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation

► The perlecan knockout mice showed severely impaired endochondral bone formation. ► In Hspg2−/− growth plates, formation of the trabecular bone was almost completely defective. ► VEGFA and MMPs expression was upregulated in Hspg2−/− growth plates. ► Vascular invasion into the hypertrophic zone was inhibited. ► Cartilage perlecan promoted activation of VEGF/VEGFR by binding to VEGFR of endothelial cells.