Carbonic Anhydrase 12 Protects Endplate Cartilage From Degeneration Regulated by IGF-1/PI3K/CREB Signaling Pathway

Zhao, Xing; Shen, Pengcheng; Li, Haidong; Yang, Yingxin; Guo, Jiandong; Chen, Shuai; Ma, Yan; Sheng, Jing; Shen, Shuying; Liu, Gang; Fang, Xiangqian

doi:10.3389/fcell.2020.595969

Cited by 8 publications

(12 citation statements)

References 62 publications

(69 reference statements)

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“…The results confirmed that transfection of CA XII siRNA could significantly reverse the increase of collagen II and aggrecan protein expression caused by HSYA in the NP cells, and weaken the inhibitory effect of HSYA on MMP-13 protein expression. The results were consistent with those from Chen et al ( 18 ) and Zhao et al ( 38 ). Therefore, we hypothesized that CA XII may be an important target for HSYA to exert the regulation of ECM homeostasis.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, they also found that overexpression of CA XII could rescue IL-1β-stimulated endplate chondrocyte apoptosis, both in vitro and in vitro ( 18 ). Furthermore, CA XII could also protect inner plate cartilage from the degradation of ECM and collagen regulated by the IGF-1/PI3K/CREB signaling pathway ( 38 ). CA XII inhibition may not only disrupt the pH, which leads to lactate accumulation in NP cells, but also reduce the protein expression level of collagen II and aggrecan ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

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Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

Yang

Liao

2021

Exp Ther Med

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Intervertebral disc degeneration (IVDD) is the main cause of lower back pain. Oxidative stress injury and degradation of the extracellular matrix (ECM) are important factors causing IVDD, while hydroxysafflor yellow A (HSYA) has significant anti-oxidative stress and anti-apoptotic effects. The present study aimed to investigate the protective role of HSYA in IVDD using nucleus pulposus (NP) cells. A Cell Counting Kit-8 assay was used to detect cell viability following HSYA and tert-Butyl hydroperoxide (TBHP) treatment. Cellular reactive oxygen species levels and the level of apoptosis were measured using flow cytometry. The concentration of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase GSH-Px were detected using ELISA. DAPI staining was performed for nuclear morphology analysis, while western blot analysis was used to detect apoptotic-and ECM-related protein expression levels. Bioinformatics analysis was used to predict the binding site between HSYA and carbonic anhydrase 12 (CA12; CA XII). NP cells were transfected withsmall interference RNA (siRNA) for CA XII downregulation. Following TBHP treatment, the level of ROS increased significantly, and the concentrations of SOD, CAT and GSH-Px were decreased. In addition, the apoptosis level of the NP cell line significantly increased following TBHP treatment. Furthermore, the expression levels of ECM-related proteins, collagen II and aggrecan were significantly decreased, and the protein expression level of MMP-13 was significantly increased. HSYA (10 µM) could effectively alleviate the effects of TBHP on NP cell apoptosis, oxidative stress damage and the expression level of ECM-related proteins. A binding site was found between HSYA and CA XII. In addition, CA XII-siRNA significantly reduced the increase in the expression level of collagen II and aggrecan proteins and decrease in the expression level of MMP-13 induced by HSYA in the NP cell line. In conclusion, HSYA could attenuate oxidative stress injury and apoptosis induced by TBHP in the NP cell line, and could improve the regulation of ECM balance.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

Yang

Liao

2021

Exp Ther Med

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“…Chothe reported that IGF1 upregulated the expressions of the sodium-dependent vitamin C transporter 2 (SVCT2), which facilitate cellular uptake of ascorbic acid from the ECM to maintain the collagen synthesis (Chothe et al, 2013). Zhao et al unveiled that the activation of the IGF1/PI3K/CREB/CA12 signaling pathway attenuated IVDD by maintaining anabolism and preventing disc cell apoptosis (Zhao et al, 2020). Furthermore, several studies have demonstrated that IGF signaling activation slows IVDD by increasing ECM synthesis, cell proliferation, and inhibiting inflammatory responses, ECM degradation, and cell apoptosis, which are primarily regulated by the PI3K/Akt and MEK/ERK pathways (Pratsinis and Kletsas, 2007;Mavrogonatou and Kletsas, 2010;Pratsinis et al, 2012;Wei et al, 2013;Liu et al, 2015;Tao et al, 2015;Xu et al, 2019;Tian et al, 2020).…”

Section: Igf Signalingmentioning

confidence: 99%

“…Several studies have shown that IGF1 can promote the synthesis of ECM (Osada et al, 1996;Gruber et al, 2004;Moon et al, 2008;Kim et al, 2010;Hayes and Ralphs, 2011;Huang et al, 2011b;Illien-Junger et al, 2012;Chothe et al, 2013;Liu et al, 2014;Tao et al, 2015;Chen et al, 2020;Zhao et al, 2020). It also prevents ECM degradation by inhibiting MMPs, which increases the amount of matrix in the intervertebral disc and delays the progression of IVDD.…”

Section: Igf Signaling Inhibits Ecm Degradation and Enhances Ecm Synthesismentioning

confidence: 99%

“…Several investigations have indicated that IGF signaling is critical in the progression of IVDD. Studies have reported that the expressions of IGF are significantly abnormal in degenerative IVD tissues and cells, and it is involved in multiple pathological processes of disc degeneration by participating in cell proliferation, programmed death, degeneration and synthesis of ECM (Tao et al, 2015;Chen et al, 2020;Zhao et al, 2020). IGF signaling is considered to be a promising approach for treatment strategies of IVDD.…”

Section: Introductionmentioning

confidence: 99%

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IGF Signaling in Intervertebral Disc Health and Disease

Lin

Tian

Peng

et al. 2022

Front. Cell Dev. Biol.

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Low back pain (LBP) is a common musculoskeletal symptom, which brings a lot of pain and economic loss to patients. One of the most common causes of LBP is intervertebral disc degeneration (IVDD). However, pathogenesis is still debated, and therapeutic options are limited. Insulin-like growth factor (IGF) signaling pathways play an important role in regulating different cell processes, including proliferation, differentiation, migration, or cell death, which are critical to the homeostasis of tissues and organs. The IGF signaling is crucial in the occurrence and progression of IVDD. The activation of IGF signaling retards IVDD by increasing cell proliferation, promoting extracellular matrix (ECM) synthesis, inhibiting ECM decomposition, and preventing apoptosis and senescence of disc cells. However, abnormal activation of IGF signaling may promote the process of IVDD. IGF signaling is currently considered to have a promising treatment prospect for IVDD. An in-depth understanding of the role of IGF signaling in IVDD may help find a novel approach for IVDD treatment.

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Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration

Ma,

Liu,

Zhang

et al. 2024

Cell Biochemistry & Function

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Low back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve a definitive cure. The cartilage endplate (CEP), a crucial nutrient‐supplying tissue of the intervertebral disc, plays a pivotal role in disc degeneration. This review examines the mechanisms underlying CEP degeneration, summarizing recent advancements in understanding the structure and function of CEP, the involvement of various signaling pathways, and the roles of cartilage endplate stem cells (CESCs) and exosomes (Exos) in this process. The aim of this review is to provide a comprehensive reference for future research on CEP. Despite progress in understanding the role of CEP in IDD, the mechanisms underlying CEP degeneration remain incompletely elucidated. Future research poses significant challenges, necessitating further investigations to elucidate the complexities of CEP.

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Carbonic Anhydrase 12 Protects Endplate Cartilage From Degeneration Regulated by IGF-1/PI3K/CREB Signaling Pathway

Cited by 8 publications

References 62 publications

Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

IGF Signaling in Intervertebral Disc Health and Disease

Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration

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