التفاصيل البيبلوغرافية
| العنوان: |
CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3ß Pathway. |
| المؤلفون: |
Jiacheng Du, Menglei Xu, Fanchen Kong, Pengfei Zhu, Yubo Mao, Yijie Liu, Hong Zhou, Zhongchen Dong, Zilin Yu, Tong Du, Ye Gu, Xiexing Wu, Dechun Geng, Haiqing Mao |
| المصدر: |
Aging & Disease; Apr2022, Vol. 13 Issue 2, p552-567, 16p |
| مصطلحات موضوعية: |
INTERVERTEBRAL disk, NUCLEUS pulposus, HYDROGEN peroxide |
| مستخلص: |
Nucleus pulposus (NP) cell (NPC) senescence is one of the main causes of intervertebral disc degeneration (IVDD). However, the underlying mechanism of NPC senescence is still unclear. The cannabinoid type 2 receptor (CB2R) is a member of the cannabinoid system and plays an important role in antioxidative stress, anti-inflammatory and antisenescence activities. In this study, we used a hydrogen peroxide (H2O2)-induced NPC senescence model and a rat acupuncture IVDD model to explore the role of CB2R in IVDD in vitro and in vivo. First, we confirmed that the expression of p16INK4a in the NP tissues of IVDD patients and rat acupuncture IVDD models obviously increased accompanied by a decrease in CB2R expression. Subsequently, we found that activation of CB2R significantly reduced the number of SA-ß-gal positive cells and suppressed the expression of p16INK4a and senescence-related secretory phenotypes [SASP, including matrix metalloproteinase 9 and 13 (MMP9, MMP13) and high mobility group protein b1 (HMGB1)]. In addition, activation of CB2R promoted the expression of collagen type II (Col-2) and SRY-Box transcription factor 9 (SOX9), inhibit the expression of collagen type X (Col-X), and restore the balance of extracellular matrix (ECM) metabolism. In addition, the AMPK/GSK3ß pathway was shown to play an important role in CB2R regulation of NPC senescence. Inhibition of AMPK expression reversed the effect of JWH015 (a CB2R agonist). Finally, we further demonstrated that in the rat IVDD model, the AMPK/GSK3ß pathway was involved in the regulation of CB2R on NPC senescence. In conclusion, our experimental results prove that CB2R plays an important role in NPC senescence. Activation of CB2R can delay NPC senescence, restore the balance of ECM metabolism, and attenuate IVDD. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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