CsA attenuates compression-induced nucleus pulposus mesenchymal stem cells apoptosis via alleviating mitochondrial

Zhiliang Li1, Songfeng Chen2, Kaige Ma1

  • 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Life Sciences
|May 11, 2018
PubMed
Abstract

Insights

Cyclosporine A (CsA) protects human nucleus pulposus mesenchymal stem cells (NP-MSCs) from compression-induced apoptosis. CsA alleviates mitochondrial dysfunction and oxidative stress, offering a potential strategy for intervertebral disc degeneration (IVDD).

Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Regenerative Medicine

Background:

  • Intervertebral disc degeneration (IVDD) is a significant cause of low back pain.
  • Mesenchymal stem cells (MSCs) are crucial for disc homeostasis, but are susceptible to mechanical stress.
  • Compression-induced apoptosis of nucleus pulposus MSCs (NP-MSCs) contributes to IVDD.

Purpose of the Study:

  • To investigate the protective effects of cyclosporine A (CsA) on NP-MSCs under compression.
  • To elucidate the mechanisms by which CsA inhibits apoptosis, focusing on mitochondrial function and oxidative stress.
  • To evaluate CsA as a potential therapeutic agent for IVDD.

Main Methods:

  • Human NP-MSCs were subjected to mechanical compression.
  • Cell viability, apoptosis ratio, and cellular ultrastructure were assessed.
  • Mitochondrial function (MPTP opening, MMP, ATP levels) and oxidative stress markers (ROS, SOD, MDA) were measured.
  • Apoptosis-associated molecules were analyzed via western blot and qRT-PCR.

Main Results:

  • Compression significantly increased NP-MSC apoptosis in a time-dependent manner.
  • CsA treatment effectively reduced compression-induced apoptosis and cell death.
  • CsA rescued compression-induced mitochondrial dysfunction, ATP depletion, and oxidative stress.

Conclusions:

  • CsA protects NP-MSCs from compression-induced apoptosis by mitigating mitochondrial dysfunction and oxidative stress.
  • These findings highlight CsA's potential as a therapeutic strategy to delay or prevent IVDD.
  • Further research into CsA's role in disc regeneration is warranted.

Related Concept Videos

Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.6K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.6K
The Nucleus01:32

The Nucleus

The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression and precisely regulates the production of proteins within the cell. In contrast, the DNA inside the mitochondria and chloroplast only carries out functions that are specific to those organelles.
Arrangement of DNA within Nucleus
The regulation of gene expression inside the nucleus is dependent on many factors, including the DNA structure. The...
104.8K
Adult Stem Cells01:33

Adult Stem Cells

Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
33.9K
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.5K