Strontium chloride prevents osteoradionecrosis of the jaw by inhibiting receptor for advanced glycation end products/transforming growth factor-beta.

Osteoradionecrosis of the jaw (ORNJ) is a severe complication following radiotherapy for head and neck cancer, which seriously affects patient quality of life. Currently, no effective preventive measures exist for ORNJ. Radiation-induced fibroatrophy is reportedly closely related to ORNJ, and Strontium (Sr) has been established to harbor anti-fibrotic properties. This study aimed to investigate whether strontium chloride (SrCl2) could prevent ORNJ by alleviating radiation-induced fibroatrophy and to elucidate its underlying mechanism. Western Blot and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR) analyses confirmed that SrCl2 could inhibit the mRNA and protein expression of alpha smooth muscle actin (α-SMA) and collagen type III alpha 1 (COL3A1) in bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. RNA Sequencing (RNA-seq) and Western blot analyses confirmed that SrCl2 inhibited the expression of proteins related to radiation-induced differentiation of BMSCs to myofibroblasts by mitigating the activation of the Receptor for Advanced Glycation End products (RAGE)/Transforming growth factor beta (TGF-β) signaling pathway. Micro-computed tomography (Micro-CT) and histological analyses confirmed that SrCl2 could prevent radiation-induced bone destruction and tissue fibrosis in vivo. In conclusion, our findings suggest that SrCl2 can reduce irradiation-induced tissue fibrosis, thereby preventing the occurrence of ORNJ. Inhibiting the radiation-induced activation of the RAGE/TGF-β signaling pathway in myofibroblasts may represent a novel therapeutic strategy for ORNJ prevention.