The Expression of Hypoxia Inducible Factor-1α and Apoptosis in Herniated Discs

Ha, Kee-Yong; Koh, In-Jun; Kirpalani, Papni Arjandas; Kim, Young‐Yul; Cho, Yunkyoung; Khang, Gilson; Han, Chang Whan

doi:10.1097/01.brs.0000219493.76081.d6

Cited by 55 publications

(50 citation statements)

References 24 publications

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“…36 In studies of human IVDs, some authors correlated the degree of apoptosis with patient age. 3,13,18,29 In our CD dog population, we could establish a similar correlation. However, the small number of dogs and the absence of age-matched subgroups in all groups do not allow extrapolating these results.…”

Section: Discussionsupporting

confidence: 60%

“…This finding is in agreement with previous results regarding the degeneration of the disc with aging. 2,28,29 One finding of our study was that the cells of the NP, which preserve the matrix, 10 showed no apoptotic activity in IVDs of non-CD dogs. These cells, referred to as notochordal cells, arise from embryonic tissue and play an important role in the formation of the spine and the NP.…”

Section: Discussionmentioning

confidence: 73%

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Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

Klauser¹,

Forterre²,

Doherr

et al. 2012

Vet Sci Develop

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Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP) was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose) polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non-chondrodystrophic dogs with poly (ADP-ribose) polymerase and cleaved caspase-3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non-chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 73%

Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

Klauser¹,

Forterre²,

Doherr

et al. 2012

Vet Sci Develop

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“…However, HIF-1a is also expressed in a number of tumours [20,21,29] where it promotes the transcription of glycolytic enzymes which switch cells from aerobic to anaerobic glycolysis. HIF-1a expression in the ovine and human IVD correlates with IVD pathology [39,115,119]. The normoxic stabilization of HIF-1a in rat NP cells drives glycolytic processes which regulate aggrecan gene expression [4].…”

Section: Integration Of Engineered Annular Constructs In Repair Envirmentioning

confidence: 99%

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

et al. 2008

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The objective of this study was to assess the impact of a landmark annular lesion model on our understanding of the etiopathogenesis of IVD degeneration and to appraise current IVD repairative strategies. A number of studies have utilised the Osti sheep model since its development in 1990. The experimental questions posed at that time are covered in this review, as are significant recent advances in annular repair strategies. The ovine model has provided important spatial and temporal insights into the longitudinal development of annular lesions and how they impact on other discal and paradiscal components such as the NP, cartilaginous end plates, zygapophyseal joints and vertebral bone and blood vessels. Important recent advances have been made in biomatrix design for IVD repair and in the oriented and dynamic culture of annular fibrochondrocytes into planar, spatially relevant, annular type structures.

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“…Apoptotic cells are induced by the Fas-mediated death pathway, in which p38α MAPK activation increases the expression of Fas and FasL proteins, as well as caspase activation (33). In herniated discs, the apoptosis of disc cells following herniation differs depending on the type of herniation, which is higher in non-contained discs when compared with contained discs (9). When IVD cells undergo apoptosis, they are phagocytosed by macrophages and disc cells, including neighboring cells within cell clusters (34).…”

Section: Discussionmentioning

confidence: 99%

“…The apoptosis of IVD cells is increased more in non-contained disc herniation than in contained disc herniation, in which the herniated nucleus pulposus penetrates the PLL and is exposed to the epidural space (9). p38 mitogen-activated protein kinase (MAPK) is hypothesized to be closely associated with inflammation and apoptosis (10,11).…”

Section: Introductionmentioning

confidence: 99%

p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats

Zhu

Liu

Yang

et al. 2016

Molecular Medicine Reports

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Abstract. The present study was performed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the non-contained and p38 MAPK inhibition (p38i) groups, two coccygeal intervertebral discs (IVDs) were removed and wounded prior to relocation into the subcutaneous space of the skin of the back. In the contained group, the cartilage endplates maintained their integrity. Furthermore, SB203580 was injected intraperitoneally into the p38i group, whereas saline was injected into the other two groups. In the non-contained group, the weight of the relocated IVDs decreased to a greater extent over time when compared with the contained and p38i groups. Phosphorylated p38, tumor necrosis factor-α, and interleukin-1β were observed to exhibit higher expression levels in the non-contained group compared with the contained and p38i groups, at weeks 1 and 4 post-surgery. The expression level of caspase-3 and the densities of apoptotic disc cells were significantly higher in the non-contained group compared with the contained and p38i groups at 4 weeks post-surgery. In conclusion, p38 MAPK induces apoptosis in IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38 MAPK may be important in spontaneous resorption of IVDs.

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The Expression of Hypoxia Inducible Factor-1α and Apoptosis in Herniated Discs

Abstract: HIF-1alpha and apoptosis physiologically occur in human beings. Their expression was the highest in the noncontained group. HIF-1alpha may play a crucial role for the survival of disc cells and resorption of the herniated disc in human intervertebral discs.

Cited by 55 publications

References 24 publications

Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats

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