Effects Of Oxygen Concentration And Culture Time On Porcine Nucleus Pulposus Cell Metabolism: An In Vitro Study

Jaworski, Lukas M.; Kleinhans, Kelsey L.; Jackson, Alicia R.

doi:10.2174/2211542007666180524120522

Cited by 7 publications

(15 citation statements)

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“…In our study, both physical hypoxia and CoCl 2 -mimetic-hypoxia upregulated the lev-els of COL2 and ACAN compared with normoxia. In addition, both groups upregulated MMP1 and upregulated the level of TIMP1, which is consistent with previous studies [35,36]. The level of MMP1 was coincident with the increased expression of HIF1α.…”

Section: Ecm Metabolism and Cell Phenotypesupporting

confidence: 92%

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

Gao

et al. 2021

Front. Biosci. (Landmark Ed)

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Objective: Nucleus pulposus cells (NPCs) are cells extracted from the intervertebral disc and are important for research into intervertebral disc degeneration (IVDD). NPCs live in an avascular and relatively hypoxic environment. Cobalt chloride (CoCl2) has been used in many cell studies to mimic hypoxia. The objective of this study was to explore the possibility of using CoCl2 to induce mimetic-hypoxia for NPCs and the comparison with hypoxia (1% O2) in vitro. Materials and methods: Rat nucleus pulposus cells of Passage 3–5 were used in this research. Cell viability, rate of cell apoptosis, ROS (reactive oxygen species) generation, cell migration, extracellular pH and extracellular matrix metabolism were determined to compare the influence of hypoxia (1% O2) and CoCl2 on NPCs. Results: We found that the effects of CoCl2 on NPCs was dose-dependent. At the proper concentration, CoCl2 could be used to elicit chemical hypoxia for nucleus pulposus cells in vitro and many biological effects, analogous to physical hypoxia (1% O2), could be achieved such as enhanced cell viability, decreased apoptosis and activated extracellular matrix metabolism. On the other hand, CoCl2 mimetic-hypoxia did not affect NPCs glycolysis and migration compared to physical hypoxia. In addition, high concentration of CoCl2 (>200 μM) is harmful to NPCs with high rates of apoptosis and ECM (extracellular matrix) degradation. Conclusions: It is feasible and convenient to use CoCl2 to induce chemical mimetic hypoxia for culturing NPCs on the premise of appropriate concentration. But in aspects of cell migration and glycolysis, CoCl2 could not achieve similar results with physical hypoxia. This study may provide a convenient method and enlightenment to induce mimetic-hypoxia for researchers studying NPCs and IVVD.

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Section: Ecm Metabolism and Cell Phenotypesupporting

confidence: 92%

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

Gao

et al. 2021

Front. Biosci. (Landmark Ed)

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“…The latest study showed that 5% and 21% oxygen concentration led to a decrease in anabolic gene expression of NPs while 1% led to an increase, indicating that hypoxia was the most suitable and biological environment to maintain the NP phenotype and normoxia (21%, O 2 , defined as HOT in this study) was a pathological environment to NP cells [27]. The increase of oxygen tension caused by abnormal neovascularization in discs is strongly related to the establishment and progression of IDD [28].…”

Section: Discussionmentioning

confidence: 50%

Increased Expression of Integrin Alpha 6 in Nucleus Pulposus Cells in Response to High Oxygen Tension Protects against Intervertebral Disc Degeneration

Zheng

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

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The destruction of the low oxygen microenvironment in nucleus pulposus (NP) cells played a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). The purpose of this study was to determine the potential role of integrin alpha 6 (ITG α6) in NP cells in response to high oxygen tension (HOT) in IVDD. Immunofluorescence staining and western blot analysis showed that the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and the IVDD rat model with mild degeneration, which were reduced as the degree of degeneration increases in severity. In NP cells, the treatment of HOT resulted in upregulation of ITG α6 expression, which could be alleviated by blocking the PI3K/AKT signaling pathway. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress and protect NP cells from HOT-inhibited ECM protein synthesis. Upregulation of ITG α6 expression by HOT contributed to maintaining NP tissue homeostasis through the interaction with hypoxia-inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, these results revealed that the increase of ITG α6 expression by HOT in NP cells might be a protective factor in IVD degeneration as well as restore NP cell function.

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“…A latest study showed that 5% and 21% oxygen concentration led to decrease in anabolic gene expression of NPs while 1% led to increase, indicating that hypoxia was the most suitable and biological environment to maintain the NP phenotype and normoxia (21%, O 2 ,defined as HOT in this study) was a pathological environment to NP cells 30 . The increasing of oxygen tension caused by abnormal neovascularization in discs is strongly related to the establishment and progression of IDD 31 .…”

Section: Discussionmentioning

confidence: 55%

“…Low back pain due to IVDD affect many individuals especially in the elderly population 2 . It often leads to the lower quality of life, which meanwhile results in direct and indirect annualized costs amounting to $50 billion in A latest study showed that 5% and 21% oxygen concentration led to decrease in anabolic gene expression of NPs while 1% led to increase, indicating that hypoxia was the most suitable and biological environment to maintain the NP phenotype and normoxia (21%, O 2 ,defined as HOT in this study) was a pathological environment to NP cells 30 .…”

Section: Discussionmentioning

confidence: 65%

Integrin α6 upregulation in nucleus pulposus cell under high oxygen tension attenuates intervertebral disc degeneration

Zheng

Zhang

et al. 2021

Preprint

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The destruction of low oxygen microenvironment played critical roles in the pathogenesis of intervertebral disk degeneration (IVDD). In this study, high oxygen tension (HOT) treatment upregulated integrin α6(ITG α6) expression, which could be alleviated by blocking PI3K/AKT signaling pathway. And the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and IVDD rat model with mild degeneration, which were reduced as degeneration degree increases. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress, and protect NP cells from HOT-inhibited ECM proteins synthesis. ITG α6 upregulation by HOT contributed to maintain a NP tissue homeostasis through the interaction with hypoxia inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, ITG α6 upregulation by HOT in NP cells might be a protective factor in IVDD as well as restore NP cell function.

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Effects Of Oxygen Concentration And Culture Time On Porcine Nucleus Pulposus Cell Metabolism: An In Vitro Study

Cited by 7 publications

References 0 publications

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

Increased Expression of Integrin Alpha 6 in Nucleus Pulposus Cells in Response to High Oxygen Tension Protects against Intervertebral Disc Degeneration

Integrin α6 upregulation in nucleus pulposus cell under high oxygen tension attenuates intervertebral disc degeneration

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