Piezocision is a new periodontal method for cutting bone more precisely than conventional methods, such as bur drilling, with 3D ultrasonic vibration power. We have conducted a study on piezocision effect on periodontal tissue in rodents. Our previous animal studies demonstrated that piezocision hastens tooth movement in rodents compared to conventional methods. The histological results showed that piezocision induces bone resorption and regeneration quickly. In addition, we observed the same effect of piezocision surgery on clinical tooth movement in collaboration with the orthodontists at BUSDM. We believe that piezocision can contribute significantly to dental therapies. However, more studies of piezocision effects are necessary for a thorough understanding. Periodontal tissue healing requires the participation of regulatory molecules, cells, and scaffold or matrix. We hypothesized that piezosurgery induces alveolar bone regeneration by uncovered procedures. In this study, we focused on the cells contributing to synthesis or repair of periodontal tissue, such as osteocytes, osteoclasts, osteoblasts, white blood cells, and periodontal ligament cells in order to close the gap between clinical knowledge and cellular mechanisms Histological analysis and MRI data indicates that piezocision surgery enhanced alveolar bone degradation in the post-operative early phase (from day1 to day7), and induced bone regeneration in the post-operative mid phase (from day14 to day28). The structure of alveolar bone was similar to controls in the late phase (day70). Serum ALP activity, a bone formation marker, was significantly increased by Piezocision surgery (p<0.05). Piezocision increasd serum CTX, a bone degradation biomarker, at post-operative 7day in the 30Hz Piezocision surgery (p<0.05). In addition, Serum PINP, a bone formation biomarker, was significantly decreased in the post-operative early phase. TUNEL assays revealed that osteocyte apoptosis was induced in alveolar bone by piezocision at post-operative 1day. Apoptosis in osteocytes induces osteoclast activity that leads to bone degradation. In previous studies piezocision induced TRAP activity in the post-operative early phase. Runx2 positive osteoblast progenitor cells were observed in the post-operative day7 and 14 as assessed by Immunofluorescence microscopy analysis. The Runx2 positive cells accumulated near the new bone formation area. The structure of collagen was observed by histological staining with Pico Sirius Red. Piezocision resulted in deteriorated collagen structure in the post-operative early phase that recovered in the post-operative mid phase. Since the collagen fibers filled in the gap between alveolar bone and roots, we stained the sections with Periostin, a specific PDL biomarker. Periostin was observed on the collagen fibers that filled in the gap between bone and root. previous studies revealed that the expression of Periostin induced TGF beta, a pivotal molecule for osteoblast differentiation. Taken together, these studies indicate that periodontal tissue responds to Piezosurgery by alveolar bone decalcification and regeneration. Further elucidation of the role of the each conducting cells (eg. osteocytes, osteoclast, osteoblast, periodontal ligament cells) after piezosurgery in the periodontal tissue may provide a new target for the treatment of periodontal disease by stimulating the return to tissue homeostasis.