Purpose: To investigate the effects of sinomenine on orthodontic tooth movement and root resorption in rats, as well as the effect of sinomenine on the osteogenesis of periodontal ligament stem cells (PDLSCs).
Methods: Fifty-four male Wistar rats were randomly divided into 3 groups: control group, 20 mg/kg sinomenine group and 40 mg/kg sinomenine group. Fifty-gram orthodontic force was applied to all groups. Each group was injected intraperitoneally with corresponding concentration of sinomenine every day. After 14 days, all rats were sacrificed. Micro-computed tomography (micro-CT) scan was used to analyze tooth movement, root resorption and alveolar bone changes. The effect on periodontal tissue was analyzed by Masson, tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining. In vitro, PDLSCs were extracted and identified. The effect of sinomenine on proliferation was determined by cell-counting kit-8. The effect of sinomenine on osteogenesis was investigated by alkaline phosphatase (ALP) activity and alizarin red staining. qPCR and Western blotting were performed to explore the effects of sinomenine on the expression levels of ALP, runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG).
Results: The tooth movement and root resorption of sinomenine groups were reduced. Sinomenine decreased trabecular spacing on compression side and increased alveolar bone volume and trabecular thickness on tension side. TRAP-positive cells in sinomenine groups decreased significantly. The expressions of TNF-α and RANKL were decreased, while the expressions of OPG, RUNX2 and osteocalcin were up-regulated. In vitro, 0.1 M and 0.5 M sinomenine enhanced ALP activity, mineral deposition and the expression of ALP, RUNX2 and OPG, and reduced the expression of RANKL.
Conclusion: Sinomenine could inhibit tooth movement, reduce root resorption, and exert a positive effect on bone formation in rats. Moreover, sinomenine promoted the osteogenesis of PDLSCs.
Graphical Abstract:

Keywords: sinomenine, tooth movement, root resorption, osteoclast, osteogenesis


中文翻译：

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青藤碱抑制大鼠正畸牙齿移动和牙根吸收并增强PDLSCs的成骨分化

目的：研究青藤碱对大鼠正畸牙移动和牙根吸收的影响，以及青藤碱对牙周膜干细胞（PDLSCs）成骨的影响。
方法：54只雄性Wistar大鼠随机分为3组：对照组、20 mg/kg青藤碱组和40 mg/kg青藤碱组。对所有组施加50克正畸力。每组每天腹腔注射相应浓度的青藤碱。14天后，处死所有大鼠。微型计算机断层扫描 (micro-CT) 扫描用于分析牙齿移动、牙根吸收和牙槽骨变化。通过Masson、抗酒石酸酸性磷酸酶（TRAP）和免疫组织化学染色分析对牙周组织的影响。在体外，PDLSCs 被提取和鉴定。青藤碱对增殖的影响通过细胞计数试剂盒8测定。通过碱性磷酸酶（ALP）活性和茜素红染色研究青藤碱对成骨的影响。
结果：青藤组的牙齿移动和牙根吸收减少。青藤碱减少了受压侧的骨小梁间距，增加了受压侧的牙槽骨体积和骨小梁厚度。青藤组TRAP阳性细胞明显减少。TNF-α和RANKL的表达降低，而OPG、RUNX2和骨钙素的表达上调。在体外，0.1 M 和 0.5 M 青藤碱增强了 ALP 活性、矿物质沉积和 ALP、RUNX2 和 OPG 的表达，并降低了 RANKL 的表达。
结论：青藤碱能抑制大鼠牙齿移动，减少牙根吸收，对骨形成有积极作用。此外，青藤碱促进PDLSCs的成骨。
图形摘要：

关键词：青藤碱, 牙齿移动, 牙根吸收, 破骨细胞, 成骨