Role of Sirt1 Plays in Nucleus Pulposus Cells and Intervertebral Disc Degeneration

Guo, Ji; Shao, Minghao; Lu, Feizhou; Jiang, Jianyuan; Xia, Xinlei

doi:10.1097/brs.0000000000001954

Cited by 51 publications

(38 citation statements)

References 45 publications

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“…Our previous studies demonstrated that SIRT1 has a protective role in IVDD 31,32 . Furthermore, several studies revealed that SIRT1 plays a key role in mitophagy and apoptosis in a variety of aging-related diseases via SIRT1-Parkin-Mitohphagy pathway [33][34][35][36][37] .…”

Section: Discussionmentioning

confidence: 96%

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

et al. 2019

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The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.

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Section: Discussionmentioning

confidence: 96%

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

et al. 2019

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“…Accumulating evidence indicates that SIRT1 has an important role in IDD and osteoarthritis (OA) pathogenesis 32 – 40 . More recently, the pivotal role of SIRT1/NF-κB pathway in age-related diseases including IVD and bone has been recognized 41 – 47 .…”

Section: Discussionmentioning

confidence: 99%

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

et al. 2018

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Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.

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“…NPMSc proliferation, stemness preservation and colony formation are decreased, whereas apoptosis is increased in individuals with Idd (22). Additionally, SIRT1 exerts a protective effect on Idd, and its expression is downregulated in the degenerating disc (23). Although multiple studies on Idd and SIRT1 or Idd and NPMScs have been conducted, only a few have focused on the interaction among these three factors, and even fewer have analyzed possible signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

Ying

Bai

et al. 2020

Int J Mol Med

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Intervertebral disc degeneration (Idd) is a condition involving disruption of the bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMScs) and Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the present study was to evaluate the roles of SIRT1 and NPMScs in Idd. First, NPMScs were harvested from patients with Idd. Then, the NPMScs were treated with a SIRT activator, and monocyte chemoattractant protein 1 (McP1) and chemokine receptor 2 (ccR2) inhibitors. Indices related to NPMSc growth, proliferation, differentiation and apoptosis were measured. Subsequently, Idd rat models were established and were transfected with NPMScs overexpressing SIRT1. NPMSc apoptosis and cartilage differentiation were detected in the rat Idd model. SIRT1 expression was found to be decreased, and the expression of McP1 and ccR2 increased in NPMScs of patients with Idd. The upregulation of SIRT1 and the downregulation of the McP1/ccR2 axis promoted cartilage differentiation and reduced the number of apoptotic NPMScs. Furthermore, McP1 reversed the progression of the cartilage differentiation of NPMScs and the inhibition of NPMSc apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of rat NPMScs overexpressing SIRT1 relieved Idd in rats. Therefore, SIRT1 overexpression improved cartilage differentiation and reduced the apoptosis of NPMScs by inactivating the McP1/ccR2 axis, thus attenuating Idd in rats.

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Role of Sirt1 Plays in Nucleus Pulposus Cells and Intervertebral Disc Degeneration

Abstract: N/A.

Cited by 51 publications

References 45 publications

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

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