MicroRNAs in Intervertebral Disc Degeneration, Apoptosis, Inflammation, and Mechanobiology

Cazzanelli, Petra; Wuertz‐Kozak, Karin

doi:10.3390/ijms21103601

Cited by 161 publications

(130 citation statements)

References 100 publications

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“…Furthermore, NF-κB signaling can be altered by specific miRNAs (e.g., miR-150 [ 283 ]), but NF-κB activation can also affect expression of numerous miRNAs (e.g., miR-640 [ 284 ]). These findings offer new therapeutic approaches as miRNAs play a crucial relevance in IVD ECM degradation, cell apoptosis, and inflammation, e.g., due to their role as post-transcriptional regulators [ 285 ].…”

Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

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Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

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Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

Self Cite

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“…Until recent developments, conservative treatment or surgical procedures were the only strategies put in place to ameliorate the clinical symptoms, due to poor understanding of the pathophysiology of IVD degeneration (2). The major goals of numerous studies include the development of etiological treatments and the reversal of the degeneration process (3).…”

Section: Introductionmentioning

confidence: 99%

Lentivirus‑mediated transfer of gene encoding fibroblast growth factor‑18 inhibits intervertebral disc degeneration

Lü

Lin

2021

Exp Ther Med

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Fibroblast growth factor 18 (FGF-18) is a well-characterized anabolic growth factor involved in cartilage homeostasis. However, the effect of FGF-18 on intervertebral disc (IVD) degeneration has not been investigated. The present study aimed to investigate the role of FGF-18 in the process of rabbit IVD degeneration. In vitro, primary nucleus pulposus cells (NPs) were cultured and transfected with a lentivirus. Tert-butyl hydroperoxide (TBHP) was used to induce apoptosis in NPs on the second passage, while overexpression of FGF-18 in NPs attenuated TBHP-induced apoptosis. A rabbit annular puncture model was generated to induce IVD degeneration in vivo. The discs were injected with an FGF-18-overexpression lentivirus or a negative control lentivirus. In the sham group, the discs were exposed and not punctured. Disc degeneration was evaluated using H&E staining and a histological grading system. Reverse transcription-quantitative PCR was used to detect the expression of the extracellular matrix-degrading enzymes matrix metalloproteinase-3 (MMP-3) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). Nucleus pulposus apoptosis was detected via western blotting, immunohistochemical methods and TUNEL staining. Histologic examination showed that disc degeneration was attenuated after FGF-18 overexpression treatment. At 8 weeks after surgery, the expression of MMP-3 and ADAMTS-5 in the annular puncture groups was higher compared with in the sham group. FGF-18 treatment inhibited the expression of MMP-3 and ADAMTS-5 at the mRNA level. Western blot assays indicated that the expression level of Bax was significantly reduced in the FGF-18 groups, and that the expression level of Bcl-2 was significantly increased compared with those in the control group. Moreover, immunohistochemical analysis indicated that the FGF-18 group exhibited a lower percentage of cleaved caspase 3-positive NPs. Quantification of the TUNEL staining demonstrated that the FGF-18 group had fewer apoptotic NPs than the control group. These findings indicated that FGF-18 could delay IVD degeneration by inhibiting the apoptosis of NPs and the expression of matrix-degrading enzymes.

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“…Therefore, regenerative strategies aim to repopulate a degenerated IVD with healthy cells (cell therapy) or stimulating the existing cells to regulate the ECM reaching an enhanced composition, quantity, and structure (biomolecule and gene therapy) [ 81 , 82 , 83 , 84 , 85 ]. ECM remodeling is crucial to control the action of biochemical mediators such as cytokines (interleukins), growth factors, and enzymes (metalloproteinases and heparanase) to ultimately stop or reverse the IVD degeneration process [ 86 , 87 , 88 , 89 ]. In the past few years, cell, biomolecule, and gene therapies have been central to the regenerative strategies ( Figure 5 ).…”

Section: Regenerative Strategiesmentioning

confidence: 99%

Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus

Tavakoli

Diwan

Tipper

2020

IJMS

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Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed.

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MicroRNAs in Intervertebral Disc Degeneration, Apoptosis, Inflammation, and Mechanobiology

Cited by 161 publications

References 100 publications

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Lentivirus‑mediated transfer of gene encoding fibroblast growth factor‑18 inhibits intervertebral disc degeneration

Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus

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