We aimed to investigate the mechanism of high mobility group box 1 (HMGB1) in the accelerated fracture healing process during Traumatic brain injury (TBI). The lateral ventricles of mice in the TBI model group were injected with adenovirus-packaged short hairpin RNA (shRNA)-HMGB1 or overexpressing (ov)-HMGB1 vector. We found HMGB1 levels were higher in bone tissue at the fracture end of TBI combined with fracture model mice. Compared with the TBI combined with fracture model mice, the mice in the ov-HMGB1 group healed faster and the expression levels of mitochondrial autophagy-related proteins were higher. Compared to the ov-HMGB1 group, mice in the ov-HMGB1 + autophagy inhibitor cyclosporin A (CsA) and ov-HMGB1 + shRNA-phosphatase and tensin homolog-induced kinase 1 (PINK1) groups showed slower healing and lower expression of mitochondrial autophagy-associated proteins. The expression of osteocalcin (OCN), SOX9, and bone morphogenetic protein (BMP)-2 in bone tissue at the fracture end of the ov-HMGB1 + shRNA-PINK1 group was lower than that in the ov-HMGB1 group. The mRNA expression levels of chondrogenic differentiation markers in bone tissue at the fracture end of the ov-HMGB1 + shRNA-PINK1 group were lower than those in the ov-HMGB1 group. Fracture healing was accelerated during TBI, especially when HMGB1 was highly expressed, and HMGB1 promote accelerated fracture healing during TBI through PINK1/Parkin-mediated mitochondrial autophagy.
Keywords: Parkin RBR E3 ubiquitin-protein ligase pathway; high mobility group box 1 (HMGB1); mitochondrial autophagy; phosphatase and tensin homolog-induced kinase 1; traumatic brain injury combined with fracture.