Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration

Han, Yingchao; Li, Xinhua; Yan, Meijun; Yang, Mingjie; Wang, Shanjin; Pan, Jie; Li, Lijun; Tan, Jun

doi:10.1016/j.bbrc.2017.03.111

Cited by 75 publications

(57 citation statements)

References 36 publications

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“…The byproducts of cellular oxidative metabolism produce reactive oxygen species like superoxide anion, hydroxyl radical, hydrogen peroxide, and nitric oxide which are implicated in numerous disorders including disc degeneration [36−38]. Excessive reactive oxygen species cause oxidative stress and activates various apoptotic signaling pathways including NF-kB and MAPK pathway (found in our study) and has been well documented in animal experiments [39,40].…”

Section: Inflammaging: the Key To Disc Degenerationsupporting

confidence: 72%

Inflammaging determines health and disease in lumbar discs—evidence from differing proteomic signatures of healthy, aging, and degenerating discs

et al. 2020

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Section: Inflammaging: the Key To Disc Degenerationsupporting

confidence: 72%

Inflammaging determines health and disease in lumbar discs—evidence from differing proteomic signatures of healthy, aging, and degenerating discs

et al. 2020

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“…Studies have reported that oxidative stress may increase the incidence of apoptosis through the mitochondria‐dependent pathway in various cell types; in addition, reactive oxygen species and oxidative stress products have been shown to increase ectopic calcification formation in cardiovascular cells . Han et al reported that oxidative stress may induce apoptosis and promote calcification in disc cartilage endplate cells . These studies suggest that oxidative stress is a common pathological factor for apoptosis and calcification in cells, including EPCs.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, CEP dysfunction, which may block the nutritional supply for disc tissues, is believed to play a vital role in IDD pathogenesis . Excessive endplate chondrocyte (EPC) apoptosis and calcification are two major processes of cartilage endplate dysfunction …”

Section: Introductionmentioning

confidence: 99%

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Zhang

Lin

Tian

et al. 2018

J Cellular Molecular Medi

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Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.

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“…Extracellular vesicles, including exosomes (Exo), microvesicles (MVs) and apoptotic bodies (Abs) can regulate the process of calcification in the arteries and heart valves. 14 It is well known that autophagy and apoptosis can increase the generation of extracellular vesicles in cells. Actually, extracellular vesicle-like structures have also been found in mineralizing cartilage.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 These extracellular vesicles participate in cellular communication between cells in joint tissues and regulate the turnover of the extracellular matrix. 14 It is well known that autophagy and apoptosis can increase the generation of extracellular vesicles in cells. A recent study indicates that Abs from chondrocytes may contribute to the pathogenic process of cartilage calcification in aging patients with osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

Yuan

et al. 2019

J Cellular Molecular Medi

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This study aimed to investigate the role of apoptotic bodies (Abs) from the oxidative stressed endplate chondrocytes in regulating mineralization and potential mechanisms. Endplate chondrocytes were isolated from rats and treated with H2O2 to induce oxidative stress. The calcium deposition for matrix mineralization in the cells was examined by histological staining. The expression levels of calcification‐related genes in individual groups of cells were determined by quantitative real time‐PCR (qRT‐PCR). Subsequently, extracellular vesicles (EVs) were purified and characterized. The effect of treatment with H2O2 and/or Abs on the mineralization, extracellular PPi metabolism and related gene expression were determined. Oxidative stress significantly increased the mineralization and promoted the generation of main Abs from endplate chondrocytes. Abs were effectively endocytosed by endplate chondrocytes and co‐localized with collagen (COL)‐II in the cytoplasm, which enhanced the mineralization, alkaline phosphatase (ALP), osteocalcin (OCN), Runt‐related transcription factor 2 (RUNX2) and COL‐I expression in endplate chondrocytes. Furthermore, treatment either H2O2 or Abs significantly decreased PPi, but increased Pi production and treatment with both further enhancing the changes in endplate chondrocytes. Similarly, treatment either H2O2 or Abs significantly decreased the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ankylosis protein (ANK) expression and ENPP1 promoter activity, but increased the tissue‐nonspecific alkaline phosphatase (TNAP) expression and TNAP promoter activity in endplate chondrocytes. Oxidative stress promoted the generation of Abs, which might enhance the oxidative stress‐mediated mineralization in endplate chondrocytes by regulating the PPi metabolism.

show abstract

Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration

Cited by 75 publications

References 36 publications

Inflammaging determines health and disease in lumbar discs—evidence from differing proteomic signatures of healthy, aging, and degenerating discs

Inflammaging determines health and disease in lumbar discs—evidence from differing proteomic signatures of healthy, aging, and degenerating discs

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

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