| 曾照辉,刘 怡,王国梁,唐晓恒,刘 玮,闫 康.姜黄素通过激活Wnt/β-catenin信号通路促进骨折愈合[J].,2021,(16):3011-3017 |
| 姜黄素通过激活Wnt/β-catenin信号通路促进骨折愈合 |
| Curcumin Promotes Fracture Healing by Activating Wnt/β-catenin Signal Pathway |
| 投稿时间：2020-12-31 修订日期：2021-01-27 |
| DOI：10.13241/j.cnki.pmb.2021.16.003 |
| 中文关键词: 姜黄素 胫骨骨折 骨折愈合 成骨细胞 Wnt/β-catenin信号通路 |
| 英文关键词: Curcumin Tibial fracture Fracture healing Osteoblast Wnt/β-catenin signal pathway |
| 基金项目:国家自然科学基金项目（81702660）；空军军医大学科技发展基金项目（2019XB039） |
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| 中文摘要: |
| 摘要 目的：探讨姜黄素治疗骨折的潜在应用价值及其对Wnt/β-catenin信号通路的可能影响。方法：本研究建立了胫骨骨折SD大鼠模型（模型组），然后应用不同剂量的姜黄素（50、100和200 mg/kg/d）治疗胫骨骨折大鼠4周。治疗4周后，通过苏木精和伊红（HE）染色评价骨折区域的形态，通过ELISA法测定大鼠血清中TGF-β、BMP-2、OC和CTX-I水平。应用不同浓度的姜黄素（0、5、10、20、和50 μM）或Wnt/β-catenin信号通路抑制剂ICG-001（10 μM）处理成骨细胞3 d，然后检测细胞的ALP活性、PCNA和COL-1的含量及Wnt /β-catenin信号通路相关分子的表达水平。结果：不同剂量的姜黄素处理组大鼠的小梁状骨和胶原明显增多。与模型组相比，不同剂量的姜黄素处理组大鼠血清中的TGF-β、BMP-2和OC水平均升高，而CTX-I水平降低（P<0.05）；与模型组相比，不同剂量的姜黄素处理组大鼠骨折区域中的COL-1阳性率升高（P<0.05），而COL-2水平未发生显著变化（P>0.05）。在药物干预3 d后，10和20 μM的姜黄素促进了细胞增殖，而100和200 μM的姜黄素抑制了细胞增殖（P<0.05）。与0 μM组比较，10 μM和20 μM的姜黄素组成骨细胞上清液中PCNA和COL-1水平及ALP活性水平均显著升高（P<0.05）。与模型组相比，不同剂量的姜黄素处理组大鼠骨折区域中的Wnt-3a和β-catenin mRNA和蛋白表达水平升高，而GSK-3β降低（P<0.05）。与姜黄素组相比，ICG-001处理后成骨细胞活力、ALP活性和β-catenin的表达水平均显著下降（P<0.05）。结论：姜黄素通过激活Wnt/β-catenin信号通路促进骨折愈合并刺激成骨细胞的增殖和分化。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the potential application value of curcumin in the treatment of fracture and its possible effect on Wnt/β-catenin signal pathway. Methods: In this study, the SD rat model of tibial fracture (Model group) was established, and then different doses of curcumin (50, 100 and 200 mg/kg/d) were used to treat tibial fracture rats for 4 weeks. After 4 weeks of treatment, the morphology of the fracture area was evaluated by hematoxylin and eosin (HE) staining. The levels of TGF-β, BMP-2, OC and CTX-I in serum of rats were determined by ELISA method. In addition, osteoblasts were treated with different concentrations of curcumin (0, 5, 10, 20, and 50 μM) or Wnt/β-catenin signal pathway inhibitor ICG-001 (10 μM) for 3 d, and then the ALP activity, PCNA and COL-1 content and the expression of Wnt/β-catenin signal pathway related molecules were detected. Results: The number of trabecular bone and collagen increased significantly in different doses of curcumin treatment group (P<0.05). Compared with model group, the levels of TGF-β, BMP-2 and OC in serum of rats treated with different doses of curcumin increased, while the level of CTX-I decreased (P<0.05). Compared with model group, the positive rate of COL-1 in fracture area of rats treated with different doses of curcumin increased (P<0.05), but the level of COL-2 did not change significantly (P>0.05). After 3 d of drug intervention, 10 and 20 μM curcumin promoted cell proliferation, while 100 and 200 μM curcumin inhibited cell proliferation (P<0.05). Compared with 0 μM group, the levels of PCNA and COL-1 and the activity of ALP in the supernatant of osteoblasts of 10 μM and 20 μM curcumin increased significantly (P<0.05). Compared with model group, the expression of Wnt-3a and β-catenin mRNA and protein in the fracture area of the rats treated with different doses of curcumin increased, while the expression of GSK-3β decreased (P<0.05). Compared with curcumin group, osteoblast viability, ALP activity and β-catenin expression levels decreased significantly after ICG-001 treatment (P<0.05). Conclusion: Curcumin promotes fracture healing and stimulates osteoblast proliferation and differentiation by activating Wnt/β-catenin signal pathway. |
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