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Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting synoviocyte activation through AMPK/NF-кB pathway

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Abstract

Objective

This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats.

Methods

Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB.

Results

We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway.

Conclusion

This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (81903619, 81703529), Natural Science Research Key Project of Anhui Provincial Education Department (KJ2019A0304, KJ2018A0231), Anhui Province Natural Science Fund (1908085MH292), and the Science Fund of Bengbu Medical College (BYKC201904, BYYCX1812, BYKY1806ZD).

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Authors and Affiliations

  1. School of Pharmacy, Bengbu Medical College, No. 2600 Donghai Avenue, Bengbu, 233000, Anhui, China

    Ying Wang, Fang Wei, Qing Wang, Xiaojin Sun, Hao Liu & Yingmei Wei

  2. Anhui BBCA Pharmaceuticals Co., Ltd., No. 6288, Donghai Avenue, Bengbu, 233000, Anhui, China

    Ying Wang, Hao Xian, Jiajia Qi, Fang Wei, Xiu Cheng, Sha Li, Qing Wang, Zhaoyang Liu, Yun Yu, Jing Zhou, Xiaojin Sun, Hao Liu & Yingmei Wei

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  1. Ying Wang
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Correspondence to Yingmei Wei.

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Wang, Y., Xian, H., Qi, J. et al. Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting synoviocyte activation through AMPK/NF-кB pathway. Inflamm. Res. 69, 569–578 (2020). https://doi.org/10.1007/s00011-020-01332-2

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  • DOI: https://doi.org/10.1007/s00011-020-01332-2

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