Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation

Castro, A. L.; Ribeiro-Machado, Cláudia; Oliveíra, Carla; Teixeira, Graciosa Q.; Neidlinger‐Wilke, Cornelia; Pereira, Paulo; Vaz, Raquel; Barbosa, Mário A.; Gonçalves, Raquel M.

doi:10.1186/s13075-021-02690-w

Cited by 13 publications

(15 citation statements)

References 55 publications

(79 reference statements)

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“…106 When the spine is subjected to axial compression, the tightly packed annulus fibrosus absorbs pressure from the NP to the AF wall. 107 Therefore, AF degeneration accelerates the progression of IDD.…”

Section: Mtor Signalling In Af and Cepmentioning

confidence: 99%

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

et al. 2022

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Intervertebral disc degeneration (IDD), an important cause of chronic low back pain (LBP), is considered the pathological basis for various spinal degenerative diseases. A series of factors, including inflammatory response, oxidative stress, autophagy, abnormal mechanical stress, nutritional deficiency, and genetics, lead to reduced extracellular matrix (ECM) synthesis by intervertebral disc (IVD) cells and accelerate IDD progression. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays a vital role in diverse degenerative diseases. Recent studies have shown that mTOR signalling is involved in the regulation of autophagy, oxidative stress, inflammatory responses, ECM homeostasis, cellular senescence, and apoptosis in IVD cells. Accordingly, we reviewed the mechanism of mTOR signalling in the pathogenesis of IDD to provide innovative ideas for future research and IDD treatment.

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Section: Mtor Signalling In Af and Cepmentioning

confidence: 99%

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

et al. 2022

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“…Mechanical factors, including compressive loading, shear stress, and vibration, can all contribute to disc degeneration [ 20 ]. In addition, structural failure (e.g., annular tear, bulging disc) also associates with IVD degeneration [ 20 , 21 ]. Inadequate metabolite transport across the end plate, aging, genetics, and metabolic disorders (e.g., obesity, diabetes) may likewise contribute to disc degeneration [ 20 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Macrophages and Intervertebral Disc Degeneration

Koroth

Buko

Abbott

et al. 2023

IJMS

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The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration.

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“…The disparity in fibril changes might be due to differences in the species and natures of IDD. Thinner and disorganized collagen I fibers are also detected in fibrotic alteration of AF [ 64 ]. He et al recently reported that collagen fibrils were thicker in aging than in punctured IVDs [ 7 ].…”

Section: Matrices In Np Fibrosismentioning

confidence: 99%

“…In addition to a change in local cell entities, reports have suggested the infiltration of extrinsic cells. Accumulation of macrophage- (CCR7 + , CD163 + [ 4 ] and CD68 + [ 69 ]) and myofibroblast-like (α-SMA + ) [ 6 , 64 , 70 ] cells were documented in degenerative NP and AF. Additionally, the migration of bone marrow-derived MSCs into NPs were noted in a mouse tail-looping IDD model [ 71 ].…”

Section: Cell Composition In Np Fibrosismentioning

confidence: 99%

Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair

Sun

Lyu

et al. 2022

IJMS

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A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such as macrophages and active fibroblasts, and the upregulation of the fibroinflammatory factors TGF-β1 and IL-1/-13. Studies have suggested a role for NP cells in fibroblastic differentiation through the TGF-βR1-Smad2/3 pathway, inflammatory activation and mechanosensing machineries. Moreover, NP fibrosis is linked to abnormal MMP activity, consistent with the role of matrix proteases in regulating tissue fibrosis. MMP-2 and MMP-12 are the two main profibrogenic markers of myofibroblastic NP cells. This review revisits studies in the literature relevant to NP fibrosis in an attempt to stratify its biochemical features and the molecular identity of fibroblastic cells in the context of IDD. Given the role of fibrosis in tissue healing and diseases, the perspective may provide new insights into the pathomechanism of IDD and its management.

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Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation

Cited by 13 publications

References 55 publications

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

Macrophages and Intervertebral Disc Degeneration

Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair

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