Ligustilide alleviated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo

2019 ◽  
Vol 69 ◽  
pp. 398-407 ◽  
Author(s):  
Ke Wang ◽  
Tingting Chen ◽  
Xiaozhou Ying ◽  
Zengjie Zhang ◽  
Zhenxuan Shao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Matrix Degradation ◽  
Nucleus Pulposus Cells ◽  
Extracellular Matrix Degradation ◽  
Induced Apoptosis

scholarly journals Oxymatrine suppresses IL-1β-induced degradation of the nucleus pulposus cell and extracellular matrix through the TLR4/NF-κB signaling pathway

2020 ◽  
Vol 245 (6) ◽  
pp. 532-541
Author(s):  
Kang Wei ◽  
Jun Dai ◽  
Zhenggang Wang ◽  
Yaping Pei ◽  
Yan Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Interleukin 6 ◽  
Intervertebral Disc Degeneration ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Matrix Degradation ◽  
Nucleus Pulposus Cells

Intervertebral disc degeneration is the main cause of low back pain. However, its pathomechanism has not been fully clarified yet. Previous studies have indicated that inflammation may lead to apoptosis of nucleus pulposus cells and break the balance between anabolism and catabolism of the nucleus pulposus extracellular matrix. The purpose of this study is to explore the mitigative effect of oxymatrine on extracellular matrix degradation and apoptosis of nucleus pulposus cells after interleukin-1 beta-induced inflammation, and its possible signaling pathway. We examined the gene and protein levels of collagen II, aggrecan, and MMPs (MMP2/3/9/13) and interleukin 6 in nucleus pulposus cells. The results demonstrated that oxymatrine could reduce extracellular matrix degradation and apoptosis of nucleus pulposus cells; interleukin-1 beta prompted the expression of MMPs and interleukin 6 through TLR4/NF-κB axis, while oxymatrine reduced the expression of MMPs and TNF-α induced by interleukin-1 beta. Moreover, TAK 242, as a small molecule inhibitor of TLR4 signaling, was used to detect the effect of oxymatrine on the TLR4/NF-κB signaling. The final experimental results show that oxymatrine could reduce the inflammatory response of nucleus pulposus cells and degradation of nucleus pulposus tissue. Oxymatrine may be a potential medicine to reduce disc inflammation and relieve intervertebral disc degeneration by inhibiting the TLR4/NF-κB signal pathway. Impact statement Currently, drug therapy is a potential treatment for patients with intervertebral disc degeneration. In the present research, oxymatrine intervenes in intervertebral disc degeneration effectively via regulating inflammation in intervertebral disc degeneration rats. Our research highlights the therapeutic potential of oxymatrine in the treatment of intervertebral disc degeneration.

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells

2018 ◽  
Vol 46 (07) ◽  
pp. 1561-1580 ◽  
Author(s):  
Zengjie Zhang ◽  
Chenggui Wang ◽  
Jialiang Lin ◽  
Haiming Jin ◽  
Ke Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Potential ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.

scholarly journals Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells

2022 ◽  
Vol 9 ◽  
Author(s):  
Chenglong Xie ◽  
Yifeng Shi ◽  
Zuoxi Chen ◽  
Xin Zhou ◽  
Peng Luo ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nuclear Translocation ◽  
Autophagic Flux ◽  
Ecm Degradation ◽  
Induced Apoptosis

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

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