Effect of Ursolic Acid on Bone Remodeling in Orthodontic Tooth Movement Model Rats by Modulating Hedgehog Signaling Pathway

doi:10.13701/j.cnki.kqyxyj.2026.01.012

Abstract

Abstract: Objective: To investigate the effect of ursolic acid (UA) on bone remodeling in orthodontic tooth movement model rats by modulating Hedgehog signaling pathway. Methods: A rat model of orthodontic tooth movement was constructed, and the successfully modeled rats were assigned into model group, L-UA, M-UA, H-UA groups (15, 30, 60 mg/kg UA by gavage), and H-UA+Cyclopamine group (60 mg/kg UA by gavage+15 mg/kg Hedgehog signaling pathway inhibitor Cyclopamine by intraperitoneal injection), each with 10 rats. Another 10 normal rats were designated as Control group. The Control group and the model group were given an equal amount of physiological saline once a day for 28 consecutive days. A vernier caliper was used to measure the distance of orthodontic tooth movement in rats. HE staining was used to observe the bone remodeling of periodontal tissue. TRAP staining was used to observe osteoclasts in rat periodontal tissue. Immunohistochemistry was applied to test the expression intensity of bone morphogenetic protein-2 (BMP-2) in periodontal tissue. Western blot was applied to test changes of Shh, Ptch-1, and Gli-1 proteins in rat periodontal tissue. Results: For the Control group, the model group showed loss of normal maxillary structure in rat tissue, widened tension side periodontal ligament, and active alveolar bone remodeling (P<0.05). For the model group, the L-UA group, M-UA group, and H-UA group showed a growth in new bone formation on the tension side of the maxilla in rats, and a gradual reduction in bone resorption cavities in a dose-dependent manner (P<0.05). For the H-UA group, the H-UA+Cyclopamine group had a narrower periodontal gap on the pressure side of the maxilla, with obvious resorption pits on the surface of the dental bone (P<0.05). For the Control group, the model group showed an increase in the number of osteoclasts in the periodontal tissue, an increase in orthodontic tooth movement distance, an increase in BMP-2 intensity in the periodontal tissue, and a downregulation of Shh, Ptch-1, and Gli-1 proteins (P<0.05). For the model group, the L-UA group, M-UA group, and H-UA group showed a decrease in the number of osteoclasts in rat periodontal tissue, a growth in orthodontic tooth movement distance, BMP-2 intensity, Shh, Ptch-1, and Gli-1 proteins in periodontal tissue (P<0.05). For the H-UA group, the H-UA+Cyclopamine group showed a growth in the number of osteoclasts in periodontal tissue, a reduction in orthodontic tooth movement distance, BMP-2 intensity, Shh, Ptch-1, and Gli-1 proteins in periodontal tissue (P<0.05). Conclusion: UA can promote bone remodeling in orthodontic tooth movement model rats by activating the Hedgehog signaling pathway.

Key words: ursolic acid, Hedgehog signaling pathway, orthodontic tooth movement, bone remodeling

XU Nuo, HAN Shuang, WANG Shichao, WANG Lili, TONG Lin, LI Wuli. Effect of Ursolic Acid on Bone Remodeling in Orthodontic Tooth Movement Model Rats by Modulating Hedgehog Signaling Pathway[J]. Journal of Oral Science Research, 2026, 42(1): 64-69.

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