CD24 identifies nucleus pulposus progenitors/notochordal cells for disc regeneration

Liu, Zhuochao; Zheng, Zhiyong; Qi, Jin; Wang, Jun; Zhou, Qi; Hu, Fangqiong; Liang, Jing; Li, Changwei; Zhang, Wei-Bin; Zhang, Xingkai

doi:10.1186/s13036-018-0129-0

Cited by 24 publications

(19 citation statements)

References 21 publications

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“…HIF-1α, a key transcription factor in hypoxic condition, plays an important role in promoting cell survival, matrix synthesis, and regulating energy metabolism, in the disc under hypoxic condition (Choi et al, 2015;Risbud et al, 2006). Through HIF-1α, hypoxia controls a host of factors, such as SDC4 (Fujita et al, 2014), CA12 (Chen et al, 2016) and CD24 (Liu et al, 2018), which contribute to maintain homeostasis of NP and protect against degeneration in hypoxic condition of the disc. Although there was no evidence to conclude that HIF-1α could enhance the expression of CD44 in NPCs, several researchers have shown that expression of CD44 correlated with hypoxia-induced gene signatures in tumours.…”

Section: Discussionmentioning

confidence: 99%

The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1α transcriptional activation of CD44 under hypoxia

Zhang¹,

Liu²,

Li³

et al. 2021

eCM

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Intervertebral disc degeneration (IDD) is the leading cause of low-back pain. Implantation of hyaluronic acid (HA) is potentially a therapeutic strategy for IDD, but its pharmacological effects and mechanism under hypoxic conditions remain unclear. In this study, the expression of extracellular matrix genes and proteins were enhanced in nucleus pulposus cells (NPCs) in the presence of HA under hypoxic condition, as shown by real-time reverse transcription-polymerase chain reaction, immunofluorescence staining, and dimethylmethylene blue assays. Moreover, the expression of CD44 was increased in the presence of both HA and hypoxia compared to either alone. Using a bioinformatic database, hypoxia inducible factor-1α (HIF-1α), a key transcription factor in the hypoxic condition, was found to have 4 predicted binding sites on the CD44 promoter. CD44 expression was significantly increased by treatment with cobalt chloride or dimethyloxalylglycine. Over-expression of HIF-1α in NPCs significantly up-regulated the expression of CD44. The binding site of HIF-1α in the CD44 promoter region, was identified by promoter truncation experiments and chromatin immunoprecipitation assays. Taken together, these results indicated that hypoxic conditions positively potentiated the ability of NPCs matrix synthesis in the presence of HA, which correlated with the increasing CD44 expression by HIF-1α transcriptional activation.

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Section: Discussionmentioning

confidence: 99%

The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1α transcriptional activation of CD44 under hypoxia

Zhang¹,

Liu²,

Li³

et al. 2021

eCM

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“…Western blot was performed as previously described 22 . The blots were incubated with antibodies against cleaved-caspase-3 (ab13847, Abcam, USA), cleavedcaspase-9 (ab202068, Abcam, USA), Bax (ab32503, Abcam, USA), Bcl-2 (ab59348, Abcam, USA), cytochrome-c (ab133504, Abcam, USA), phospho-JNK (5599, CST, USA), JNK (9252, CST, USA), LC3B (ab48394, Abcam, USA), Beclin-1 (ab207612, Abcam, USA), P62 (ab109012, Abcam, USA) or Atg-5 (ab108327, Abcam, USA) at 4°C overnight.…”

Section: Western Blotmentioning

confidence: 99%

Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

Liu

Wang

et al. 2021

Cell Death Dis

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In this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

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“…It should be noted that CD24 was detected to express in NPCs, and CD24+ NPCs decreased with IVDD severity 71 . Previously, CD24+ NPCs were identified as progenitors in NP 72 . In humans, the percentage of CD24+NPCs decreased significantly with aging or degeneration, which dropped to less than 10% in elderly adults or severely degenerated discs 73 .…”

Section: Discussionmentioning

confidence: 98%

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

Yang

et al. 2021

Preprint

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Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain. However, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, we first reported a comprehensive single-cell resolution transcriptional landscape of human NP. Six novel human nucleus pulposus cell (NPCs) populations were identified by distinct molecular signatures. The potential functional differences among NPC subpopulations were analyzed at the single-cell level. Predictive genes, transcriptional factors, and signal pathways with respect to degeneration grades were analyzed. We reported that fibroNPCs, one of our identified subpopulations, might be a population for NP regeneration. CD90+NPCs were observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). We uncovered CD11b, OLR1, and CD24 as surface markers of NP-derived G-MDSCs. The G-MDSCs were also found to be enriched in mildly degenerated (grade I and II) NP tissues compared to severely degenerated (grade III and IV) NP tissues. Their immunosuppressive function and protective effects for NPCs were revealed . Collectively, this study revealed the NPC type complexity and phenotypic characteristics in NP, providing new insights and clues for IVDD treatment.

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CD24 identifies nucleus pulposus progenitors/notochordal cells for disc regeneration

Cited by 24 publications

References 21 publications

The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1α transcriptional activation of CD44 under hypoxia

The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1α transcriptional activation of CD44 under hypoxia

Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

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