Adequate blood supply around bone grafts is crucial in periodontal regenerative surgery. Research suggests that cortical perforation during surgery can stimulate angiogenesis and cell migration, increase blood supply to the surgical site, and promote local tissue regeneration. However, the effects of perforation on the local tissue microenvironment and the molecular mechanisms by which corticotomy promotes bone regeneration remain unclear. In this study, a rat model was established to investigate the effect of cortical perforation on osteogenesis around bone grafts. Different groups of alveolar bone were ground to prepare conditioned medium, and the effect on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) was observed in vitro. Finally, we focused on the nerve growth factor (NGF) with the most obvious difference and verified the role of NGF and its potential molecular mechanism in vivo and in vitro. The results showed that osteogenesis around the local bone graft was more pronounced after corticotomy. Additionally, using a tissue-conditioned medium promoted the osteogenic differentiation of PDLSCs, while the expression of NGF increased locally after corticotomy. Further investigation using exogenous NGF or NGF inhibitors confirmed that NGF plays a crucial role in promoting osteogenesis around the bone graft, specifically through activating the JNK/c-Jun pathway. These findings suggest that targeting the mechanism by which cortical perforation promotes bone regeneration could lead to new therapeutic strategies for enhancing bone augmentation in regenerative surgery.