Otubain 2 stabilizes TNF‑receptor associated factor 3 to accelerate bone fracture healing

Increased incidence of traumatic fracture markedly effects the quality of life of patients. Using a rat model of femur fracture, the present study aimed to investigate the effects of otubain 2 (OTUB2), a deubiquitinating enzyme, on bone fracture healing. Bone marrow mesenchymal stem cells (BMSCs) were harvested from the marrow cavity of rat femurs and tibiae and subsequently subjected to osteogenic differentiation in vitro. Results of the present study revealed that lentivirus‑mediated OTUB2 overexpression accelerated rat bone fracture healing, potentiated fracture callus formation and cartilaginous ossification and regulated the expression of proteins associated with bone remodeling. In addition, OTUB2 overexpression facilitated the osteogenic differentiation and mineralization of BMSCs and promoted the expression of TNF‑receptor associated factor 3 (TRAF3) both in vivo and in vitro. Co‑immunoprecipitation analysis was used to verify the physical interaction between OTUB2 and TRAF3 and further results demonstrated that OTUB2 reduced the ubiquitination of TRAF3. The results of the present study also demonstrated that TRAF3 knockdown repressed the OTUB2‑induced osteogenic differentiation and mineralization of BMSCs. Collectively, these results demonstrated that OTUB2 may stabilize TRAF3 to accelerate bone fracture healing.