CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3β Pathway

Du, Jianjun; Xu, Menglei; Kong, Fanchen; Zhu, Ping; Mao, Yubo; Liu, Yijie; Zhao, Hong; Dong, Zhongchen; Yu, Zilin; Du, Tong; Gu, Ye; Wu, Xiexing; Geng, Dechun; Mao, Haiqing

doi:10.14336/ad.2021.1025

Cited by 41 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study rea rmed naringin's therapeutic potential in exploring the probable involvement of AMPK in paraspinal muscle degeneration associated with discogenic low back pain [44,45]. In the context of paraspinal muscle degeneration, crucial factors include in ammation, oxidative stress, and mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 52%

Naringin Ameliorates IL-6 Mediated mitochondrial dysfunction and skeletal muscle degeneratio via AMPK/Nrf-2 pathway

Gao,

Wang,

Zhang

et al. 2024

Preprint

View full text Add to dashboard Cite

Ethnopharmacological relevance: Paraspinal muscle degeneration often arises as a hazardous consequence of intervertebral disc degeneration (IVDD). This degeneration correlates with oxidative stress and mitochondrial dysfunction. This study investigated the therapeutic potential of naringin in managing paraspinal muscle degeneration associated with disc degeneration. Materials and methods: C2C12 cells were stimulated with IL-6 to establish an in vitro model of skeletal muscle degeneration for assessing the protective impact of naringin on skeletal muscle. The most effective concentration of naringin in C2C12 cells was identified through a CCK8 assay. The antioxidant prowess of naringin was evaluated via biochemical methods and Elisa. The influences of naringin and IL-6 on apoptosis, mitochondrial function, and associated signaling pathways were examined using cytometry, ROS detection, western blot, and transmission electron microscopy. Results: Our findings demonstrated a significant reduction in discogenic paraspinal degeneration with naringin therapy. Naringin glycosides notably enhanced the expression of key proteins involved in both muscle anabolism and catabolism, including MAFbx, MuRF1, MyoD, and MyoG.Moreover, naringin contributed to maintaining redox homeostasis by augmenting antioxidant activity and preventing excessive ROS peroxide accumulation. To impede paraspinal muscle degeneration, naringin upregulated MyoD and MyoG expression while downregulating MAFbx and MuRF1 through the activation of AMPK/Nrf-2 signaling pathway. Conclusion: These findings underscore naringin's robust therapeutic potential in enhancing mitochondrial activity, regulating oxidative stress, and halting paraspinal muscle degeneration.

show abstract

Section: Discussionmentioning

confidence: 52%

Naringin Ameliorates IL-6 Mediated mitochondrial dysfunction and skeletal muscle degeneratio via AMPK/Nrf-2 pathway

Gao,

Wang,

Zhang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…During the process of degeneration, excessive decomposition and destruction of the ECM in the microenvironment of the NP tissue disrupt the anabolic balance of the ECM, resulting in decrease in the water retention capacity of NP tissue, causing further shrinkage of NP tissue and acceleration of IVDD pathogenesis [ 40 ]. ECM catabolism in the NP primarily involves the ADAMTS and matrix metalloproteinases (MMP) families, while the ECM is mainly composed of type II collagen and proteoglycans [ 41 , 42 ]. MMP-3 is a gelatinase that degrades denatured collagen and gelatin.…”

Section: Resultsmentioning

confidence: 99%

Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment

Qingxin,

Kai,

Dandan

et al. 2023

J Nanobiotechnol

View full text Add to dashboard Cite

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

show abstract

“…During the progression of IDD, NP cells senescence escalates, thereby stimulating the release of senescence-associated secretory phenotype (SASP) [ 26 ]. This gives rise to an inflammatory microenvironment, further intensifying the senescence process in adjacent cells [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Omilancor mitigates the senescence of nucleus pulposus cells induced by DDP through targeting MAP2K6

Yafeng,

Xinpeng,

Rong

et al. 2024

Aging

View full text Add to dashboard Cite

Purpose: This study explores the potential of Omilancor in treating Intervertebral Disc Degeneration (IDD) through MAP2K6 targeting. Methods: We analyzed mRNA microarray datasets to pinpoint MAP2K6 as a key regulator implicated in IDD progression. Follow-up studies demonstrated that cisplatin (DDP) could prompt cellular senescence in vitro by upregulating MAP2K6 expression. Through molecular docking and other analyses, we identified Omilancor as a compound capable of binding to MAP2K6. This interaction effectively impeded the cellular senescence induced by DDP. Results: We further showed that administration of Omilancor could significantly alleviate the degeneration of IVDs in annulus fibrosus puncture-induced rat model. Conclusions: Omilancor shows promise as a treatment for IDD by targeting MAP2K6-mediated cellular senescence.

show abstract

CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3β Pathway

Cited by 41 publications

References 49 publications

Naringin Ameliorates IL-6 Mediated mitochondrial dysfunction and skeletal muscle degeneratio via AMPK/Nrf-2 pathway

Naringin Ameliorates IL-6 Mediated mitochondrial dysfunction and skeletal muscle degeneratio via AMPK/Nrf-2 pathway

Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment

Omilancor mitigates the senescence of nucleus pulposus cells induced by DDP through targeting MAP2K6

Contact Info

Product

Resources

About