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Sinomenine Attenuates Cartilage Degeneration by Regulating miR-223-3p/NLRP3 Inflammasome Signaling

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Abstract

Sinomenine (SIN) has been shown to protect against IL-1β-induced chondrocyte apoptosis in vitro. However, the role of SIN in the anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA) mouse model and its underlying molecular mechanisms remain unclear. In the present study, the protective effect of SIN on ACLT-induced articular cartilage degeneration and IL-1β-induced chondrocyte apoptosis miR-223-3p/NLRP3 signaling regulation was investigated. Safranin O staining was performed to evaluate the pathological changes of articular cartilage. Chondrocyte apoptosis was measured with Annexin V-fluorescein isothiocyanate/polyimide (annexin V-FITC/PI) staining using flow cytometry. Gene and protein expression were detected by RT-qPCR and Western blotting, respectively. SIN administration markedly improved articular cartilage degradation in mice undergoing ACLT surgery. In addition, SIN treatment downregulated the levels of inflammatory cytokines and the protein expression of NLRP3 inflammasome components and upregulated the expression of miR-223-3p in OA mice and IL-1β-stimulated chondrocytes. In vitro, we found that NLRP3 was a direct target of miR-223-3p, and overexpression of miR-223-3p blocked IL-1β-induced apoptosis and the inflammatory response in chondrocytes. These findings indicate that miR-223-3p/NLRP3 signaling could be used as a potential target of SIN for the treatment of OA.

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Abbreviations

SIN:

sinomenine

ACLT:

anterior cruciate ligament transection

OA:

osteoarthritis

TNF-α:

tumor necrosis factor-α

IL-1β:

interleukin-1β

TLR4:

toll-like receptor 4

NF-κB:

nuclear factor kappa B

TRAF6:

tumor necrosis factor receptor-associated factor 6

NLRP3:

NOD-like receptor family, pyrin domain containing 3

ASC:

caspase-recruitment domain

3′-UTR:

3′-untranslated regions

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Funding

This research was supported by the Medical Science Research Fund of Dalian City of China (Grant no. 1812021).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Second Clinical College, Dalian Medical University, No. 222 Zhongshan Road, Dalian, 116011, China

    Hai-Chao Dong, Pei-Nan Li, Xin Xu, Hong Zhang, Gang Liu, Lian-Jie Zheng & Peng Li

  2. Dalian love cubic Health Management Co., Ltd, Dalian, 116000, China

    Chang-Jian Chen

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  1. Hai-Chao Dong
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Contributions

Study design: HAI-CAO DON; Literature research, Data acquisition, and Data analysis: HAI-CAO DON, PEI-NAN LI, CHANG-JIAN CHEN, XIN XU, HONG ZHANG, GANG LIU, LIAN-JIE ZHENG, PENG LI; Manuscript preparation and Manuscript editing: HAI-CAO DONG, PEI-NAN LI and CHANG-JIAN CHEN; Manuscript review: T HAI-CAO DON; Cell experiments: CHANG-JIAN CHEN, XIN XU and HONG ZHANG; Animal experiments: GANG LIU, LIAN-JIE ZHENG and PENG LI. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hai-Chao Dong.

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Ethics Approval and Consent to Participate

This study was permitted by the Ethics Committee of the Dalian Medical University (Dalian, China) on June 1st in 2017 (Approval number 20170019a).

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The authors declare that they have no competing interests.

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Dong, HC., Li, PN., Chen, CJ. et al. Sinomenine Attenuates Cartilage Degeneration by Regulating miR-223-3p/NLRP3 Inflammasome Signaling. Inflammation 42, 1265–1275 (2019). https://doi.org/10.1007/s10753-019-00986-3

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