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Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway.
Cell Physiol Biochem 2018; 45(3):1252-1269CP

Abstract

BACKGROUND/AIMS

Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration.

METHODS

Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis.

RESULTS

In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells.

CONCLUSION

LY could serve as a potential drug for treating IVD disease.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

29448253

Citation

Wang, Gangliang, et al. "Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration By Inhibiting NF-κB Signalling Pathway." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 45, no. 3, 2018, pp. 1252-1269.
Wang G, Huang K, Dong Y, et al. Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway. Cell Physiol Biochem. 2018;45(3):1252-1269.
Wang, G., Huang, K., Dong, Y., Chen, S., Zhang, J., Wang, J., ... Fan, S. (2018). Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 45(3), pp. 1252-1269. doi:10.1159/000487457.
Wang G, et al. Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration By Inhibiting NF-κB Signalling Pathway. Cell Physiol Biochem. 2018;45(3):1252-1269. PubMed PMID: 29448253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway. AU - Wang,Gangliang, AU - Huang,Kangmao, AU - Dong,Yangxin, AU - Chen,Shuai, AU - Zhang,Jianfeng, AU - Wang,Jiying, AU - Xie,Ziang, AU - Lin,Xianfeng, AU - Fang,Xiangqiang, AU - Fan,Shunwu, Y1 - 2018/02/09/ PY - 2017/06/29/received PY - 2018/01/09/accepted PY - 2018/2/16/pubmed PY - 2018/3/20/medline PY - 2018/2/16/entrez KW - Cartilaginous endplate KW - Interleukin-1β KW - Intervertebral disc degeneration KW - Lycorine KW - Macrophage-inhibitory factor KW - Matrix-degrading protease SP - 1252 EP - 1269 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 45 IS - 3 N2 - BACKGROUND/AIMS: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. METHODS: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. RESULTS: In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. CONCLUSION: LY could serve as a potential drug for treating IVD disease. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29448253/Lycorine_Suppresses_Endplate_Chondrocyte_Degeneration_and_Prevents_Intervertebral_Disc_Degeneration_by_Inhibiting_NF_κB_Signalling_Pathway_ L2 - https://www.karger.com?DOI=10.1159/000487457 DB - PRIME DP - Unbound Medicine ER -