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| Research of anthocyanins relieve osteoarthritis pain in mice by up-regulating IGFBP-4 which inhibits synovial Wnt/β-catenin signaling pathway |
| Hits 65 Download times 8 Received:October 29, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.03.13 |
| Key Words
osteoarthritis pain;IGFBP-4;Wnt/β-catenin pathway;anthocyanins |
| Author Name | Affiliation | E-mail | | WANG Rui | North China University of Science and Technology, Tangshan 063210, China | | | ZHAO Xuemei | North China University of Science and Technology, Tangshan 063210, China | | | LI Da | North China University of Science and Technology, Tangshan 063210, China | | | QIAO Yuxue | North China University of Science and Technology, Tangshan 063210, China | | | JIANG Xiaohua | North China University of Science and Technology, Tangshan 063210, China
Hebei Key Laboratory for Chronic Diseases, Tangshan 063210, China | jiangxiaohua@ncst.edu.cn |
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| Abstract
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| [Objective] To explore the mechanism of anthocyanins in relieving the pain of osteoarthritis mice. [Methods] The OA model were constructed in C57/BL6 mice by injecting iodoacetic acid. The OA model was treated with over expression of anthocyanin and insulin growth factor binding protein 4（IGFBP-4） and knockdown adenovirus. Randomly divided into 8 groups with 10 animals in each group：normal group，sham group，OA group，anthocyanins treatment（AC） group，IGFBP-4 overexpression（BP4+OA） group，IGFBP-4 overexpression control（CON267+OA） group，IGFBP-4 knockdown（BP4-OA） group，IGFBP-4 knockdown control（CON098+OA） group. The successful construction of IGFBP-4 adenovirus model was observed with small animal in imaging system. HE staining evaluated whether the model was successfully constructed. The changes of the mechanical pain threshold and thermal pain threshold were evaluated by Von Frey and hot plate experiments. Substance P content in serum was detected by ELISA. The morphological changes of spinal dorsal root ganglion（DRG） were evaluated by Nissl’s staining. Immunohistochemical staining was used to detect the expression of transient receptor potential vanillate receptor 1（TRPV1） in DRG. Western blot was used to detect TRPV1 protein expression in DRG and IGFBP-4，Wnt3a，β-catenin，TNF-α and IL-6 in synovial. [Results] Fluorescence signals were observed in the knee joint of BP4+OA，CON267+OA，BP4-OA and CON098+OA groups；the radiation efficiency of BP4+OA group and BP4-OA group were higher than that of no-load control group（P＜0.05）. In OA group，CON267+OA group and CON098+OA group，there were synovial inflammatory cell infiltration，connective tissue hyperplasia，and cartilage surface erosion defect；the pathological changes of synovial membrane and cartilage were improved in AC group and BP4+OA group. The pathological injury of synovium and cartilage in BP4-OA group was further aggravated. Compare with Sham group，OA group，CON267+OA group and CON098+OA group of PWMT and PWTL were reduced. Compare with OA group，PWMT and PWTL in AC group and BP4+OA group were prolonged than OA group；PWMT and PWTL were shortened in BP4-OA group（P＜0.05）. Some of the neurons disappeared，the cytoplasm was vacuolar and Nil staining became shallow in OA group，CON267+OA group and CON098+OA group；DRG morphological change was reduced in AC group and BP4+OA group；DRG morphological damage of in BP4-OA group was further aggravated. Substance P content and TRPV1 in DRG in OA group were higher than that in Sham group；substance P content and TRPV1 in DRG in AC group were lower than that in OA group. Substance P content and TRPV1 in DRG in BP4+OA group were lower than that in CON267+OA group and OA group . Substance P content and TRPV1 in DRG in BP4-OA group were higher than that in CON098+OA and OA groups，and significantly higher than that in BP4+OA and AC groups（P＜0.05）. TNF-α，IL-6，Wnt3a，β-catenin in synovial in OA group were higher than that in Sham group. TNF-α，IL-6，Wnt3a，β-catenin in synovial in AC group were lower than that in OA group. TNF-α，IL-6，Wnt3a，β-catenin in synovial in BP4+OA group were lower than that in CON267+OA group and OA group. TNF-α，IL-6，Wnt3a，β-catenin in synovial in BP4-OA group were higher than that in CON098+OA and OA groups，and significantly higher than that in BP4+OA and AC groups（P＜0.05）. IGFBP-4 in synovial in OA group was higher than that in sham group. IGFBP-4 in synovial in AC group was higher than those in OA group，and significantly higher than that in Sham group. IGFBP-4 in synovial in BP4+OA group was higher than that in CON267+OA group. IGFBP-4 in synovial in BP4-OA group was significantly lower than that in CON098+OA，and significantly lower than that in BP4+OA and AC groups（P＜0.05）. [Conclusion] Anthocyanins may inhibit Wnt/β-catenin pathway by up-regulating the expression of synovial IGFBP-4，reduce inflammatory response，and relieve peripheral sensitization and pain in KOA mice. |
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