Acid-sensitive ion channel 1a mediates osteoarthritis chondrocyte senescence by promoting Lamin B1 degradation

Ding, Jie; Chen, Yong; Zhao, Yingjie; Chen, Fan; Dong, Lei; Zhang, Hailin; Hu, Wei; Li, Shufang; Zhou, Ren‐Peng; Hu, Wei

doi:10.1016/j.bcp.2022.115107

Cited by 7 publications

(6 citation statements)

References 66 publications

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“…Lamin B1 expression is reduced by ASIC1a during the degradation of autophagy-dependent proteins (Ding et al, 2022). In this study, Lamin B1 was confirmed as a nucleophagy substrate upon DNA damage, and LC3 combined with Lamin B1 to induce nucleophagy that degrades Lamin B1 and leaked nuclear DNA.…”

Section: Discussionmentioning

confidence: 51%

“…Arginine starvation can induce nuclear DNA leakage upon DNA damage, and nuclear inner membrane (Lamin A/C) can partially fuse with autophagosome membrane, suggesting that DNA damage can evoke autophagy‐mediated degradation of leaked nuclear DNA (Changou et al, 2014). Lamin B1 expression is reduced by ASIC1a during the degradation of autophagy‐dependent proteins (Ding et al, 2022). In this study, Lamin B1 was confirmed as a nucleophagy substrate upon DNA damage, and LC3 combined with Lamin B1 to induce nucleophagy that degrades Lamin B1 and leaked nuclear DNA.…”

Section: Discussionmentioning

confidence: 99%

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UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

Fan,

Lou,

Jin

et al. 2024

Journal Cellular Physiology

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Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen–glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin‐related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2‐D08 (a small‐molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy‐related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2‐D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3‐Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

Fan,

Lou,

Jin

et al. 2024

Journal Cellular Physiology

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“…Targeting cellular senescence therapeutic strategies can effectively alleviate osteoarthritis progression [ 34 ]. In knee OA, acid-sensitive ion channel 1a promoted the degradation of Lamin B1 protein by inducing autophagy, thereby promoting chondrocyte senescence [ 44 ]. Another study showed that the decreased expression of miR-26b-5p during the pathogenesis of OA promoted the expression of Asporin.…”

Section: Discussionmentioning

confidence: 99%

Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration

et al. 2023

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Objective Lumbar facet joint (LFJ) degeneration is one of the main causes of low back pain (LBP). Mechanical stress leads to the exacerbation of LFJ degeneration, but the underlying mechanism remains unknown. This study was intended to investigate the mechanism of LFJ degeneration induced by mechanical stress. Methods Here, mice primary chondrocytes were used to screen for key microRNAs induced by mechanical overloading. SA-β-gal staining, qRT-PCR, western blot, and histochemical staining were applied to detect chondrocyte senescence in vitro and in vivo. We also used a dual-luciferase report assay to examine the targeting relationship of miRNA-325-3p (miR-325-3p) and Trp53. By using NSC-207895, a p53 activator, we investigated whether miR-325-3p down-regulated trp53 expression to reduce chondrocyte senescence. A mice bipedal standing model was performed to induce LFJ osteoarthritis. Adeno-associated virus (AAV) was intraarticularly injected to evaluate the effect of miR-325-3p on facet joint degeneration. Results We observed chondrocyte senescence both in human LFJ osteoarthritis tissues and mice LFJ after bipedally standing for 10 weeks. Mechanical overloading could promote chondrocyte senescence and senescence-associated secretory phenotype (SASP) expression. MicroRNA-array analysis identified that miR-325-3p was obviously decreased after mechanical overloading, which was further validated by fluorescence in situ hybridization (FISH) in vivo. Dual-luciferase report assay showed that miR-325-3p directly targeted Trp53 to down-regulated its expression. MiR-325-3p rescued chondrocyte senescence in vitro, however, NSC-207895 reduced this effect by activating the p53/p21 pathway. Intraarticular injection of AAV expressing miR-325-3p decreased chondrocyte senescence and alleviated LFJ degeneration in vivo. Conclusion Our findings suggested that mechanical overloading could reduce the expression of miR-325-3p, which in turn activated the p53/p21 pathway to promote chondrocyte senescence and deteriorated LFJ degeneration, which may provide a promising therapeutic strategy for LFJ degeneration.

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Section: Lmnb1 Affects Cell Senescence Through T Cellsmentioning

confidence: 99%

“…LMNB1 affects cell senescence through acid-sensitive ion channels Ding et al [27] studied the mechanism of acid-sensitive ion channel 1a (ASIC1a) in chondrocyte senescence and osteoarthritis (OA). The results show that ASIC1a, as a rich proton-activated cation channel in chondrocytes, can not only act as a perceptron to accept pH changes in the joint cavity but also regulate its changes simultaneously [27]. In addition, LMNB1 can be used as a substrate for autophagy, which is induced by ASIC1A-mediated autophagy pathway-dependent protein degradation; in the OA rat model, blocking ASIC1a can protect cartilage tissue, restore LMNB1 expression level, and inhibit chondrocyte senescence [27].…”

Section: Lmnb1 Affects Cell Senescence Through T Cellsmentioning

confidence: 99%

Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors

Lv,

Wang,

Zhou

et al. 2024

Cell Death Discov.

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Nuclear lamin B1 (LMNB1) is a member of the nuclear lamin protein family. LMNB1 can maintain and ensure the stability of nuclear structure and influence the process of cell senescence by regulating chromatin distribution, DNA replication and transcription, gene expression, cell cycle, etc. In recent years, several studies have shown that the abnormal expression of LMNB1, a classical biomarker of cell senescence, is highly correlated with the progression of various malignant tumors; LMNB1 is therefore considered a new potential tumor marker and therapeutic target. However, the mechanism of action of LMNB1 is influenced by many factors, which are difficult to clarify at present. This article focuses on the recent progress in understanding the role of LMNB1 in cell senescence and malignant tumors and offers insights that could contribute to elucidating the mechanism of action of LMNB1 to provide a new direction for further research.

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Acid-sensitive ion channel 1a mediates osteoarthritis chondrocyte senescence by promoting Lamin B1 degradation

Cited by 7 publications

References 66 publications

UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration

Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors

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