HIF1A Alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy

He, Ruijun; Wang, Zhe; Cui, Min; Liu, Sheng; Wu, Wei; Chen, Mo; Wu, Yongchao; Qu, Yanji; Lin, Hui; Chen, Sheng; Wang, Baichuan; Shao, Zengwu

doi:10.1080/15548627.2021.1872227

Cited by 122 publications

(100 citation statements)

References 88 publications

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“…In contrast, we established the opposite effect of serpinc1 in promoting the apoptosis of HCC cells because it can change the ubiquitination sites of various proteins related to autophagy and apoptosis pathway. For example, the HIF1A/BNIP3 axis, the main autophagy and apoptosis regulator under hypoxia ( 31 ), was significantly upregulated at the ubiquitinated sites after serpinc1 is overexpressed. Further studies are warranted to confirm whether the impaired HIF1A/BNIP3 axis is the cause of serpinc1-induced apoptosis in HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner

Luo

et al. 2021

Front. Oncol.

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Serpinc1 is a serine protease inhibitor in the coagulation cascade, but its role in tumor biology remains obscure. Here, we report an unexpected role of serpinc1 in suppression of hepatocellular carcinoma (HCC). In HCC patients, the mRNA and protein expression of serpinc1 is upregulated, which is negatively correlated with tumor grade, and has a better prognosis than patients with low serpinc1. In addition, patients with high expression of serpinc1 generally have a better tumor immune microenvironment, accompanied by changes in multiple immune cells and mediators. In particular, tumor-promoting M2 macrophages are negatively correlated with serpinc1 expression and the prognosis of HCC patients. In vitro experiments further show that overexpression of serpinc1 inhibits the growth of HCC cells (HepG2 and SMMC7721) by inducing apoptosis. Accordingly, cell co-culture experiments reveal the direct role of serpinc1-overexpressed HCC cells in inhibiting the formation of M2 macrophages. Subsequent unbiased quantitative proteomic and ubiquitinome analyses identify that multiple poly-ubiquitination of proteins involved in signal pathways (such as autophagy, apoptosis, lactate metabolism, and VEGF signaling) are regulated by serpinc1. Overall, these findings establish a serpinc1-dependent ubiquitin-proteasome system to control apoptosis and antitumor immunity.

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Section: Discussionmentioning

confidence: 99%

Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner

Luo

et al. 2021

Front. Oncol.

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“…The density of NP cells in degenerated disks decreased compared to normal disk tissue (Liu C. et al, 2020). Since excessive mechanical load can induce apoptosis of NP-derived stem cells, some people try to delay intervertebral disk degeneration by anti-apoptosis (He et al, 2021), and promoting NP cell proliferation has also been proven to inhibit intervertebral disk degeneration (Cui et al, 2020). In recent years, with the deepening of research, the phenotypic characteristics of NP cells and the relationship between cell senescence and intervertebral disk degeneration have gradually been considered (Choi et al, 2015;.…”

Section: Pathophysiology Of Intervertebral Disk Degenerationmentioning

confidence: 99%

“…Chen et al found that by triggering autophagy, cell senescence and apoptosis could also be decreased, ultimately improving intervertebral disk degeneration (Chen et al, 2018). In subsequent studies, many people have reduced cell senescence and apoptosis by upregulating autophagy, thus maintaining intervertebral disk repair and delaying degeneration (He et al, 2021;Hu et al, 2021).…”

Section: Pathophysiology Of Intervertebral Disk Degenerationmentioning

confidence: 99%

Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

Bai

Tian

et al. 2021

Front. Bioeng. Biotechnol.

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Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.

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“…But few studies have focused on the impact of CoCl 2 on NPCs cell viability. He et al [38] performed CCK-8 tests and found that 10 µM to 100 µM CoCl 2 was safe in mimetic-hypoxia for the in vitro study of NPCs. Jiang et al [39] treated NPCs with 200 µM CoCl 2 for mimetic hypoxia.…”

Section: Cell Viabilitymentioning

confidence: 99%

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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HIF1A Alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy

Cited by 122 publications

References 88 publications

Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner

Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner

Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

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

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