Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor α (TNF-α) Signaling Pathway

Ding, Fan; Li, Xia

doi:10.12659/msm.924587

Cited by 12 publications

(8 citation statements)

References 50 publications

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“…Previous studies have shown that TNF- α plays a conclusive role in the occurrence and development of IDD; thus, inhibiting inflammation effectively can ameliorate the progression of IDD [ 15 – 17 , 45 – 47 ]. It has been demonstrated that aloin is effective in reducing the production of inflammatory and proinflammatory factors [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Aloin Regulates Matrix Metabolism and Apoptosis in Human Nucleus Pulposus Cells via the TAK1/NF-κB/NLRP3 Signaling Pathway

Chen

Qiu

et al. 2022

Stem Cells International

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Intervertebral disc degeneration (IDD) is a degenerative disease that is characterized by decreased matrix synthesis and extra degradation, nucleus pulposus cells (NPCs) apoptosis, and infiltration of inflammatory factors. Aloin, a colored compound from aloe plants, has been shown to be effective against skeletal degenerative diseases, but it is unclear whether it is protective against IDD. Herein, we investigated the role of aloin in NPCs. In our study, the upregulation of proinflammatory factors, apoptosis, and unbalanced matrix metabolism were observed in degenerative NP tissues. We found that aloin had a curative effect on extracellular matrix metabolism and apoptosis in TNF-alpha- (TNF-α-) treated NPCs by inhibiting oxidative stress and the proinflammatory factor expression. Further investigation revealed that aloin treatment suppressed the TAK1/NF-κB pathway. Moreover, the expression level of the NLPR3 inflammasome was downregulated after aloin treatment in TNF-α-treated NPCs. In summary, our results demonstrated that aloin treatment can reverse TNF-α-induced unbalanced matrix metabolism and apoptosis of NPCs via the TAK1/NF-κB/NLRP3 axis. This study supports that aloin can be a promising therapeutic agent for IDD.

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Section: Discussionmentioning

confidence: 99%

Aloin Regulates Matrix Metabolism and Apoptosis in Human Nucleus Pulposus Cells via the TAK1/NF-κB/NLRP3 Signaling Pathway

Chen

Qiu

et al. 2022

Stem Cells International

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“…A few studies have investigated the association of COX2 with IVDD in animal models and in vitro cell culture. In rat [ 45 ] and dog [ 46 ] models with induced IVD degeneration, increased expression of COX2 has been found in degenerated discs. In disc cell culture, IL-1 β [ 34 , 47 ] and TNF- α [ 48 ] have been found to elevate inflammatory gene expression including COX2.…”

Section: Discussionmentioning

confidence: 99%

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration

Liu

Liang

Deng

et al. 2021

Mediators of Inflammation

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Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

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“…A recent study demonstrated that deletion of progranulin in mice accelerates disc degeneration, at least in part, by upregulating IL-17 expression (S. Wang, Wei, et al, 2018). On the other hand, administration of apigenin, an edible plant-derived flavonoid, attenuates IL-17 levels and consequently leads to alleviation of IDD in a rat model (Ding & Li, 2020). Low magnitude of tensile stress also mitigates disc degeneration in rats, along with decreased expression of IL-17 in the disc (Han et al, 2015).…”

Section: The Promotive Effect Of Il-17 On Iddmentioning

confidence: 99%

IL‐17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications

Tan

Liu

et al. 2022

Cell Biology International

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Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor α (TNF-α) Signaling Pathway

Cited by 12 publications

References 50 publications

Aloin Regulates Matrix Metabolism and Apoptosis in Human Nucleus Pulposus Cells via the TAK1/NF-κB/NLRP3 Signaling Pathway

Aloin Regulates Matrix Metabolism and Apoptosis in Human Nucleus Pulposus Cells via the TAK1/NF-κB/NLRP3 Signaling Pathway

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration

IL‐17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications

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