Strontium Chloride Prevents ORNJ By Inhibiting Rage/TGF-Β

The purpose of this study is to investigate whether strontium chloride (SrCl2) can prevent osteoradionecrosis of the jaw (ORNJ) by alleviating radiation-induced tissue fibrosis and to further study its specific mechanism. The key indicators of radiation-induced bone marrow-derived mesenchymal stem cells (BMSCs) differentiation into myofibroblasts were analyzed by RT-qPCR and Western blot. RNA sequencing analysis and Western blot analysis were performed to investigate the potential mechanism of SrCl2 inhibits BMSCs differentiation into myofibroblasts. ORNJ animal model was established in Sprague-Dawley rats (9 week old, 300g-320g, male). Micro-CT and histology analysis were used to assess the prevention of bone destruction and tissue fibrosis by SrCl2 in vivo. All animal experiments were approved by the Animal Ethics Committee of Speaker's Institution. SrCl2 could inhibit the mRNA and protein expression of α-SMA and COL3A1 of BMSCs in vitro. SrCl2 prevented the protein expression related to radiation-induced differentiation of BMSCs to myofibroblasts by inhibiting the activation of the receptor for advanced glycation end products (RAGE)/ transforming growth factor beta (TGF-β) signaling pathway. SrCl2 could prevent radiation-induced bone destruction and tissue fibrosis in vivo. SrCl2 can reduce irradiation-induced tissue fibrosis to prevent the occurrence of ORNJ. Inhibiting the radiation-induced activation of the RAGE/TGF-β signaling pathway in myofibroblasts may be a novel therapeutic strategy for preventing ORNJ.