Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs

Ghannam, Malik; Jumah, Fareed; Mansour, Shaden; Samara, Amjad; Alkhdour, Saja; Alzuabi, Muayad; Aker, Loai; Adeeb, Nimer; Massengale, Justin; Oskouian, Rod J.; Tubbs, R. Shane

doi:10.1002/ca.22822

Cited by 22 publications

(16 citation statements)

References 180 publications

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“…With the increase in the population of elderly people around the world, disc degeneration has attracted more and more attention [39]. Traditional surgical treatments are able to alleviate pain symptoms in most instances but are not able to biologically restore normal disc functions.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. Methods: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. Results: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. Conclusion: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

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Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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“…NP is a flexible sphere located in the center of IVD and is surrounded by AF in the anterior, posterior, left and right directions. EP is attached on the superior and inferior NP [3]. The factors that damage NP, AF or EP may lead to the degeneration of IVD.…”

Section: Introductionmentioning

confidence: 99%

Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation

Zhang

Chen

et al. 2019

Aging

128

109

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The inflammatory-associated factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine (melatonin) is a natural hormone secreted by the pineal gland which has been shown to participate in several physiological and pathological progresses, such as aging, anti-inflammation, anti-apoptosis and autophagy regulation. However, the effects of melatonin on IVD remain unclear. In the present study, we treated human nucleus pulposus cells (NPCs) with melatonin and discovered that melatonin could modulate extracellular matrix (ECM) remodeling induced by IL-1β by enhancing collagen II and aggrecan expression levels and by downregulating matrix metalloproteinase-3 (MMP-3) levels. These findings were verified by western blot and immunofluorescence assays. Intraperitoneal injection of melatonin mitigated IVDD in the rat tail puncture model. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue and Celium red staining methods were adopted to evaluate IVDD grades, the structural integrity of nucleus pulposus (NP) and annulus fibrosus (AF) and the damage and calcification of the cartilage endplate. Melatonin reduced inflammatory cell aggregation and the release of the inflammatory factors IL-1β, IL-6, TNF-α as determined by immunohistochemistry. In conclusion, the present study demonstrated that melatonin could modulate ECM remodeling by IL-1β in vitro and attenuate the IVDD and induction of inflammation in a rat tail puncture model in vivo. The data demonstrated that melatonin may contribute to the restoration processs of IVD following damage and may be used as a potential novel therapy for IVDD.

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“…Under such a condition of insufficient oxygen and nutrients, NP and AF cells form low cell density after adulthood. Therefore, once injured, IVD only regenerates slowly in a limited way (Ghannam et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Recent advances of hydrogel‐based biomaterials for intervertebral disc tissue treatment: A literature review

Zheng

2021

J Tissue Eng Regen Med

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Low back pain is an increasingly prevalent symptom mainly associated with intervertebral disc (IVD) degeneration. It is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and annulus fibrosus fissure formatting, which finally results in the IVD herniation and related clinical symptoms. Hydrogels have been drawing increasing attention as the ideal candidates for IVD degeneration because of their unique properties such as biocompatibility, highly tunable mechanical properties, and especially the water absorption and retention ability resembling the normal NP tissue. Numerous innovative hydrogel polymers have been generated in the most recent years. This review article will first briefly describe the anatomy and pathophysiology of IVDs and current therapies with their limitations. Following that, the article introduces the hydrogel materials in the classification of their origins. Next, it reviews the recent hydrogel polymers explored for IVD regeneration and analyses what efforts have been made to overcome the existing limitations. Finally, the challenges and prospects of hydrogel‐based treatments for IVD tissue are also discussed. We believe that these novel hydrogel‐based strategies may shed light on new possibilities in IVD degeneration disease.

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Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs

Cited by 22 publications

References 180 publications

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation

Recent advances of hydrogel‐based biomaterials for intervertebral disc tissue treatment: A literature review

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