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Strontium ion attenuates osteoarthritis through inhibiting senescence and enhancing autophagy in fibroblast-like synoviocytes

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Abstract

Osteoarthritis (OA) mainly occurs in the elderly population and seriously affects their quality of life (QOL). Strontium (Sr) ions have shown positive effects on bone tissue and are promising for OA treatment. However, the adequate treatment dosage and underlying mechanisms are unclear. This study investigated the effects and underlying mechanisms of different concentrations of Sr ions in a mouse model of OA induced by destabilization of the medial meniscus (DMM) surgery. DMM-induced OA mice received intra-articular injections of different concentrations of Sr ions, and a suitable concentration of Sr ions was found to improve OA. Furthermore, we investigated the mechanism by which Sr ions mediate senescence and autophagy in fibroblast-like synoviocytes (FLSs) in the synovial tissues of DMM-induced OA mice. OA mice treated with 10 µl of 5 mmol/L SrCl2 showed the greatest improvement in pain-related behavior and cartilage damage. In addition, in vivo and in vitro experiments revealed that Sr ions inhibit senescence and improve the autophagic function of FLSs. We also found that enhancement of the autophagic function of FLSs could effectively slow down senescence. Therefore, we show that Sr ions through the AMPK/mTOR/LC3B-II signal axis improve FLSs autophagy function and delay FLSs senescence, and furthermore, improve OA. These results suggest that senescence and autophagy function of FLSs may serve as promising targets for OA treatment, and that Sr ions may inhibit OA progression through these two targets.

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Acknowledgements

This study was supported by the Military Medical Innovation Engineering Project (no.17cxz004). The funder had no role in study design, data collection, data analysis, interpretation, or writing the report.

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Authors and Affiliations

  1. Department of Orthopedics, Xijing Hospital, The Air Force Military Medical University, No. 127 Changle West Road., Xi’an, Shaanxi, China

    Binghui Liao, Ming Ding, Yingchun Wang, Hu Xu & Lei Shangguan

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  1. Binghui Liao
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  2. Ming Ding
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  3. Yingchun Wang
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  4. Hu Xu
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Contributions

Liao and Shangguan designed the study; Binghui Liao, Ming Ding, Yingchun Wang, and Hu Xu performed the experiments; Binghui Liao and Hu Xu analyzed the data; and Binghui Liao and Lei Shangguan wrote the paper. All authors reviewed and approved the final manuscript.

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Correspondence to Lei Shangguan.

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This study was not a clinical trial, and did not involve human participants. All animal experimental procedures were approved by the Animal Research Committee of the Air Force Military Medical University, People’s Republic of China.

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Liao, B., Ding, M., Wang, Y. et al. Strontium ion attenuates osteoarthritis through inhibiting senescence and enhancing autophagy in fibroblast-like synoviocytes. Mol Biol Rep 50, 1437–1446 (2023). https://doi.org/10.1007/s11033-022-08112-7

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