Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells

Chen, Weisin; Yasen, Miersalijiang; Wang, Hanquan; Zhuang, Chenyang; Wang, Zixiang; Lu, Shunyi; Jiang, Libo; Lin, Hong

doi:10.1186/s40360-022-00633-y

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…Pro inflammatory cyclines such as IL‐1β, IL‐17, and TNF‐α are associated with inter regional disc generation, and their expression is significantly increased in degenerative inter regional disc issue (Chen, Yasen, et al, 2022; Tan et al, 2022; Zhang, He, et al, 2019). Nuclear factor kappa B (NF‐κB) is a multifunctional transcription factor that plays an important role in the regulation of inflammatory response, cell promotion, and apoptosis (Zhu et al, 2019).…”

Section: Cell Autophagy and Iddmentioning

confidence: 99%

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

Tao,

Yu,

et al. 2024

Cell Biology International

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Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy‐related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy‐related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

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Section: Cell Autophagy and Iddmentioning

confidence: 99%

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

Tao,

Yu,

et al. 2024

Cell Biology International

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“…Another recent study focused on the use of cxb in rat NP cells, which showed promising results in restoring extracellular matrix formation and minimizing oxidative stress by activating the mammalian target of rapamycin and downstream proteins to accelerate autophagy machinery. However, this effect has not been investigated in AF cells [11,18,19].…”

Section: Celecoxib's Effect On Il-1β-treated Hafcsmentioning

confidence: 99%

Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells

Häne

Eglauf

et al. 2023

Eur Spine J

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Purpose This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. Methods hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model. Results IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation. Conclusion Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.

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“…Of the two direct functions of STING, it is clear that the inflammatory activity of STING needs to be suppressed in the treatment of IVDD, while the upregulation of autophagy can improve IVDD. Exercise, certain endogenous hormones, or drugs can activate autophagy to protect NP cells from aging and apoptosis, and inhibit ECM degradation ( 154 , 155 ). As described in the first section of this article, autophagy mediates STING signal attenuation.…”

Section: Sting and Age-related Diseases In The Musculoskeletal Systemmentioning

confidence: 99%

STING signaling in inflammaging: a new target against musculoskeletal diseases

Song

et al. 2023

Front. Immunol.

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Stimulator of Interferon Gene (STING) is a critical signaling linker protein that plays a crucial role in the intrinsic immune response, particularly in the cytoplasmic DNA-mediated immune response in both pathogens and hosts. It is also involved in various signaling processes in vivo. The musculoskeletal system provides humans with morphology, support, stability, and movement. However, its aging can result in various diseases and negatively impact people’s lives. While many studies have reported that cellular aging is a leading cause of musculoskeletal disorders, it also offers insight into potential treatments. Under pathological conditions, senescent osteoblasts, chondrocytes, myeloid cells, and muscle fibers exhibit persistent senescence-associated secretory phenotype (SASP), metabolic disturbances, and cell cycle arrest, which are closely linked to abnormal STING activation. The accumulation of cytoplasmic DNA due to chromatin escape from the nucleus following DNA damage or telomere shortening activates the cGAS-STING signaling pathway. Moreover, STING activation is also linked to mitochondrial dysfunction, epigenetic modifications, and impaired cytoplasmic DNA degradation. STING activation upregulates SASP and autophagy directly and indirectly promotes cell cycle arrest. Thus, STING may be involved in the onset and development of various age-related musculoskeletal disorders and represents a potential therapeutic target. In recent years, many STING modulators have been developed and used in the study of musculoskeletal disorders. Therefore, this paper summarizes the effects of STING signaling on the musculoskeletal system at the molecular level and current understanding of the mechanisms of endogenous active ligand production and accumulation. We also discuss the relationship between some age-related musculoskeletal disorders and STING, as well as the current status of STING modulator development.

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Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells

Cited by 5 publications

References 57 publications

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells

STING signaling in inflammaging: a new target against musculoskeletal diseases

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