TGF-β signaling in intervertebral disc health and disease

Chen, Sheng; Liu, Sheng; Ma, Kaige; Zhao, Lei; Lin, Hui; Shao, Zengwu

doi:10.1016/j.joca.2019.05.005

Cited by 103 publications

(87 citation statements)

References 112 publications

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“…TGFβ3 has been shown to maintain the phenotype of disc cells in organ culture by elevating the levels of activated ERK1/2, which can regulate the expression of TGFβRI and TGF‐β‐RII . Activation of ERK1/2 also suggests that TGFβ could potentially signaling through the non‐canonical pathway . However, it is also possible that TGFβ could exert an anabolic effect via activation of SMADS2/3 …”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β Enhances Tissue Formation by Passaged Nucleus Pulposus Cells In Vitro

Ashraf

Chatoor

Chong

et al. 2019

Journal Orthopaedic Research

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The nucleus pulposus (NP) is composed of NP and notochord cell. It is a paucicellular tissue and if it is to be used as a source of cells for tissue engineering the cell number will have to be expanded by cell passaging. The hypothesis of this study is that passaged NP and notochordal cells grown in three-dimensional (3D) culture in the presence of transforming growth factor β (TGFβ) will show enhanced NP tissue formation compared with cells grown in the absence of this growth factor. Bovine NP cells isolated by sequential enzymatic digestion from caudal intervertebral discs were either placed directly in 3D culture (P0) or serially passaged up to passage 3 (P3) prior to placement in 3D culture. Serial cell passage in monolayer culture led to de-differentiation, increased senescence and oxidative stress and decreases in the gene expression of NP and notochordal associated markers and increases in de-differentiation markers. The NP tissue regeneration capacity of cells in 3D culture decreases with passaging as indicated by diminished tissue thickness and total collagen content when compared with tissues formed by P0 cells. Immunohistochemical studies showed that type II collagen accumulation appeared to decrease. TGFβ1 or TGFβ3 treatment enhanced the ability of cells at each passage to form tissue, in part by decreasing cell death. However, neither TGFβ1 nor TGFβ3 were able to restore the notochordal phenotype. Although TGFβ1/3 recovered NP tissue formation by passaged cells, to generate NP in vitro that resembles the native tissue will require identification of conditions facilitating retention of notochordal cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β Enhances Tissue Formation by Passaged Nucleus Pulposus Cells In Vitro

Ashraf

Chatoor

Chong

et al. 2019

Journal Orthopaedic Research

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“…Although the pathogenesis of LBP is poorly understood, intervertebral disc degeneration (IVDD) has been proposed to be the major cause of LBP 2,3 . IVDD is characterized by increased oxidative stress, the degradation of extracellular matrix (ECM) and apoptosis, and decreased autophagy or mitophagy 4,5 .…”

Section: Introductionmentioning

confidence: 99%

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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“…It has been reported that the activity of MMPs is not limited to matrix cleavage; they also modulate the in ammatory response [27], which may explain why degenerative discs were also sensitive to pro-in ammatory stimuli [28]. It has been reported that TGF-β was a major up-stream regulator of collagens and proteoglycans [29]. However, TGF-β gene transcription was not affected in this study.…”

Section: Discussionmentioning

confidence: 49%

A Momentary Impact Injury of Vertebral Endplates, even without Structural Disruption, Initiates Disc Degeneration In Vitro.

Sun

Wang

Jiang

et al. 2020

Preprint

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Background ： It has been acknowledged that the intervertebral disc degeneration(IDD) is associated with an aberrant cell-medicated response to structural failures, such as vertebral burst fracture, radial fissures, and endplate fracture. However, whether a momentary impact injury of the endplates without structural disruption, is sufficiently to initiate disc degeneration remains elusive. This study was to further evolve an in vitro momentary impact injury model of IDD and to investigate if a momentary impact load of the endplates without structural disruption could initiate IDD. Methods. Rat spinal segments (from L1/2 to L5/6, n=54) were harvested and randomly assigned into three groups: Control (n=18), Low Impact (12 J/cm 3 , n=18) and High Impact (25 J/cm 3 , n=18). Samples in both of the impact groups were subjected to axial momentary impact load using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology and real-time PCR. Results: The discs in both of the impact groups showed significant degenerative changes at 14 days, both of which showed much higher histological scores and up-regulation of the catabolic (MMP-9, MMP-13) genes transcription than that of the control group ( P ＜0.05). The discs with endplate fracture compared to that with intact endplate also showed strongly up-regulated catabolic (MMP-9, MMP-13) genes transcription, and more significant degenerative changes based on the histological scoring ( P ＜0.05). Conclusion: This study demonstrated that a momentary impact load (12 J/cm 3 ) on the spinal segments of the rats could initiate IDD at 14 days after injury and not only endplate fracture but also a momentary impact injury without structural disruption could also promote IDD.

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TGF-β signaling in intervertebral disc health and disease

Cited by 103 publications

References 112 publications

Transforming Growth Factor β Enhances Tissue Formation by Passaged Nucleus Pulposus Cells In Vitro

Transforming Growth Factor β Enhances Tissue Formation by Passaged Nucleus Pulposus Cells In Vitro

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

A Momentary Impact Injury of Vertebral Endplates, even without Structural Disruption, Initiates Disc Degeneration In Vitro.

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