Osteogenic protein-1 alleviates high glucose microenvironment-caused degenerative changes in nucleus pulposus cells

Liu, Ziming; Zhang, Zhiwen; Zhang, Ali; Zhang, Fan; Du, Wennan; Zhang, Yongqiang; Zhang, Rongfeng; Xu, Jiagang; Wu, Xiangkun; Zhang, Chengmin; Li, Ning; Tan, Qi; Huang, Wei

doi:10.1042/bsr20190170

Cited by 11 publications

(18 citation statements)

References 36 publications

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“…Because normal AF cell viability is responsible for maintaining of the ECM in AF tissue, inhibiting high glucose-induced AF cell apoptosis may be a potential way to retard disc degeneration in DM patients. In line with us, several previous studies have shown that high glucose significantly affected biological behaviors of intervertebral disc cells, such as promoting cell apoptosis [15,19], accelerating autophagy [37], decreasing matrix biosynthesis [14] and inducing cellular senescence [15,38]. Together, these studies indicate that a high glucose environment is harmful to the healthy cellular activities of disc cells.…”

Section: Discussionsupporting

confidence: 83%

“…DM often induces many complications including cardiovascular issue, renal failure and neuropathy [9]. Several studies have reported that DM is a potential etiological factor of intervertebral disc degeneration [10][11][12][13][14][15]. Moreover, some researchers have demonstrated that high glucose can promote apoptosis of disc cartilage endplate cells and notochordal cells, and ultimately accelerate the progression of disc degeneration [16,17].…”

Section: Introductionmentioning

confidence: 99%

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High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress

2020

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. However, how DM affects annulus fibrosus (AF) biology remains unclear. The present study was aimed to investigate the effects and mechanism of high glucose on AF cell biology. Rat AF cells were cultured in baseline medium and culture medium with 0.2 M glucose. The inhibitor 4-PBA was added along with the high glucose culture medium to study the role of endoplasmic reticulum (ER) stress in this process. Compared with the control cells, high glucose significantly increased cell apoptosis ratio and caspase-3/9 activity, up-regulated mRNA/protein expression of Bax and caspase-3/cleaved caspase-3, but down-regulated mRNA/protein expression of Bcl-2. Moreover, high glucose increased mRNA and protein expression of CHOP, ATF-6 and GRP78. However, once ER stress was inhibited by the inhibitor 4-PBA in the high glucose group, cell apoptosis ratio and caspase-3/9 activity were decreased, mRNA/protein expression of Bax and caspase-3/cleaved caspase-3 was down-regulated, but mRNA/protein expression of Bcl-2 was up-regulated. In conclusion, high glucose condition can promote AF cell apoptosis through inducing ER stress. The present study helps us understand the mechanism of disc degeneration in DM patients.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress

2020

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“…There are two types of DM (type 1 DM and type 2 DM) with approximately 90% of DM patients are type 2 DM [1]. Accumulating evidence has shown that DM is a crucial effecter in the progression of intervertebral disc degeneration [2][3][4][5][6]. The morbidity of disc degeneration is much higher in DM patients than that in non-DM patients [7].…”

Section: Introductionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.

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“…Recently, several studies demonstrated that diabetes mellitus (DM) is a risk factor of IDD in a DM patient, and DM patients have a higher incidence and a faster progress of IDD than non-DM patients [2][3][4][5]. Furthermore, several basic researches reported that DM-associated hyperglycemia is harmful to the health biology of disc cells [6][7][8][9][10][11][12][13][14]. Currently, many researchers have managed to investigate the pathogenesis of IDD in DM patients.…”

Section: Introductionmentioning

confidence: 99%

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

Wang

Xue

et al. 2021

BioMed Research International

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Diabetes mellitus- (DM-) associated hyperglycemia promotes apoptosis of disc nucleus pulposus (NP) cells, which is a contributor to intervertebral disc degeneration (IDD). Melatonin is able to protect against cell apoptosis. However, its effects on apoptosis of NP cell in a high-glucose culture remain unclear. The purpose of the present study was to investigate the effects and molecular mechanism of melatonin on NP cell apoptosis in a high-glucose culture. NP cells were cultured in the baseline medium supplemented with a high-glucose concentration (0.2 M) for 3 days. The control cells were only cultured in the baseline medium. Additionally, the pharmaceutical inhibitor LY294002 was added along with the culture medium to investigate the possible role of the PI3K/Akt pathway. Apoptosis, autophagy, and activity of the PI3K/Akt pathway of NP cells among these groups were evaluated. Compared with the control NP cells, high glucose significantly increased cell apoptosis ratio and caspase-3/caspase-9 activity and decreased mRNA expression of Bcl-2, whereas it increased mRNA or protein expression of Bax, caspase-3, cleaved caspase-3, cleaved PARP, and autophagy-related molecules (Atg3, Atg5, Beclin-1, and LC3-II) and decreased protein expression of p-Akt compared with the control cells. Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. This study provides new theoretical basis of the protective effects of melatonin against disc degeneration in a DM patient.

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Osteogenic protein-1 alleviates high glucose microenvironment-caused degenerative changes in nucleus pulposus cells

Cited by 11 publications

References 36 publications

High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress

High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

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