A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells

Abstract

It has been hypothesized that intervertebral disc degeneration is initiated by degeneration of the cartilage endplate (CEP), which is characterized by cartilage ossification. CEP-derived stem cells (CESCs), with the potential for chondro-osteogenic differentiation, may be responsible for the balance between chondrification and ossification in the CEP. The CEP remains in an avascular and hypoxic microenvironment; the present study observed that hypoxia was able to markedly inhibit the osteogenic differentiation of CESCs. This tissue-specific CESC differentiation in response to a hypoxic microenvironment was physiologically important for the prevention of ossification in the CEP. In order to study the hypoxia-regulated mechanisms underlying osteogenic differentiation of CESCs, a Human Transcriptome Array 2.0 was used to detect differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) during the osteogenic differentiation of CESCs under hypoxia, compared with those induced under normoxia. High-throughput analysis of DEGs and ASGs demonstrated that genes in the complement pathway were enriched, which may be a potential mechanism underlying hypoxia inhibition of CESCs osteogenesis. The results of the present study may provide a basis for future mechanistic studies regarding gene expression levels and alternative splicing events during the hypoxia-regulated inhibition of osteogenesis, which may be helpful in identifying targets for CEP degeneration therapy.

Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

“…A shorter exposure (3–14 days), applied in two studies, increased RUNX2 gene expression [32,34]. RUNX2 protein expression decreased in the five reviewed studies [27,39,48,49,53], which applied 5–21 days of sustained hypoxia at 1–2% PiO 2 . Overall, data from mRNA expression analysis could differ from protein expression by the post-translational modification of osteogenic biomarkers that may be a critical step dependent on the duration of hypoxia [26].…”

“…According to the origins of different tissues, MSCs show altered differentiation in response to hypoxia [48]. Osteogenesis may only be induced in periodontal ligament MSCs [83] under sustained hypoxic conditions but inhibited in bone marrow and adipose MSCs [50,57,84,85].…”

Carbohydrate sulfotransferase 3 (CHST3) overexpression promotes cartilage endplate‐derived stem cells (CESCs) to regulate molecular mechanisms related to repair of intervertebral disc degeneration by rat nucleus pulposus

“…Seven weeks after transplantation, CESCs was found to be osteogenic and differentiated. Sixteen weeks after implantation, CESCs was found to differentiate into chondroid‐like cells and promote disc repair 29 . These studies suggest that CESCs can respond to a variety of biomaterials to further explore the downstream regulation mechanism can lay a foundation for the application of CESCs.…”

APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer

“…Alternative splicing events (ASEs) and regulated alternative splicing events (RASEs) between the samples were de ned and quanti ed using the ABL pipeline [13]. In short, the detection of ABL, as 10 types of ASEs, was based on splice junction reads, including exon skipping (ES), alternative 5' splice site (A5SS), alternative 3'splice site (A3SS), intron retention (IR), mutually exclusive exons (MXE), mutually exclusive 5'UTRs (5pMXE), mutually exclusive 3'UTRs (3pMXE), cassette exon, A3SS&ES, and A5SS&ES.…”