Naringin promotes angiogenesis in bone fracture healing via TAS2R39-Ca²⁺-autophagy axis

Bone fracture, a widespread bone defect disease, is often caused by mechanical forces and requires long-term healing. Angiogenesis is essential for the repair of various bone defects, with the transport function of blood vessels serving as a key determinant of successful osteogenic regeneration. This study aimed to clarify the angiogenic effects of naringin and investigate the molecular mechanism. We constructed TAS2R39‑deficient HUVECs and established a young mouse tibial fracture model to explore how naringin activates TAS2R39 to promote angiogenesis.

Immunofluorescence staining, western blot and RT-qPCR were performed to detect the expression of TAS2R39 and autophagy. Wound healing assay, tube formation assay, western blot and RT-qPCR were performed to detect angiogenesis of HUVECs. mRNA-seq was performed to explored potential mechanism. Flow cytometry, immunofluorescence staining and western blot were employed to analysis Ca2 + signaling. Micro-CT and immunofluorescence staining were used to detect angiogenesis and osteogenesis of naringin in vivo.

We confirmed angiogenic effect of naringin and observed TAS2R39 activation in naringin-treated HUVECs. Through TAS2R39 knocked-down and inhibitors, we observed and confirmed that naringin activated TAS2R39 and decreased intercellular Ca²⁺ elevation thereby promoting cellular autophagy and ultimately enhancing the angiogenesis of HUVECs.

Naringin promotes angiogenesis by upregulating TAS2R39, lowering intracellular Ca²⁺, and enhancing autophagy. This TAS2R39-Ca²⁺-autophagy axis represents a novel mechanism for fracture repair in young individuals.