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Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol trisphosphate receptor signaling

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Abstract

Intra-articular injection of glucocorticoids (GCs) has been widely used in the management of osteoarthritis and rheumatoid arthritis. Nevertheless, several studies showed that GCs had toxic effects on chondrocytes as well as synovial cells. Previously we reported the protective role of autophagy in the degeneration of meniscal tissues. However, the effects of GCs on autophagy in the meniscal cells have not been fully elucidated. To investigate whether GCs can regulate autophagy in human meniscal cells, the meniscal cells were cultured in vitro and exposed in the presence of dexamethasone. The levels of apoptosis and autophagy were investigated via flow cytometry as well as western blotting analysis. The changes of the aggrecanases were measured using real-time PCR. The role of autophagy in dexamethasone-induced apoptosis was investigated using pharmacological agents and RNA interference technique. An agonist of inositol 1,4,5-trisphosphate receptor (IP3R) was used to investigate the mechanism of dexamethasone-induced autophagy. The results showed that dexamethasone induced autophagy as well as apoptosis in normal human meniscal cells. Using RNA interference technique and pharmacological agents, our results showed that autophagy protected the meniscal cells from dexamethasone-induced apoptosis. Our results also indicated that dexamethasone increased the mRNA levels of aggrecanases. This catabolic effect of dexamethasone was enhanced by 3-MA, the autophagy inhibitor. Furthermore, our results showed that dexamethasone induced autophagy via suppressing the phosphorylation of IP3R. In summary, our results indicated that autophagy protected meniscal cells from GCs-induced apoptosis via inositol trisphosphate receptor signaling.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81101379, 81472118,81171705) and the Natural Science Fund of the Shanghai Jiao Tong University School of Medicine (11XJ21022).

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The authors have declared no conflicts of interest.

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    Authors and Affiliations

    1. Department of Orthopedic Surgery, Xinhua Hospital, 1665 Kongjiang Road, 200092, Shanghai, China

      Chao Shen, Gui-Quan Cai, Jian-Ping Peng & Xiao-Dong Chen

    2. Department of Geriatrics, Xinhua Hospital, 1665 Kongjiang Road, 200092, Shanghai, China

      Wen Gu

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    1. Chao Shen
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    2. Wen Gu
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    Correspondence to Xiao-Dong Chen.

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    Chao Shen and Wen Gu have contributed equally to this study.

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    Shen, C., Gu, W., Cai, GQ. et al. Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol trisphosphate receptor signaling. Apoptosis 20, 1176–1186 (2015). https://doi.org/10.1007/s10495-015-1146-9

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    • DOI: https://doi.org/10.1007/s10495-015-1146-9

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