JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2

  • 0Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Bone & Joint Research +

|

February 25, 2025

|

February 25, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cellular senescence accumulates in chronic shoulder tendinopathies, correlating with tissue degeneration. Inhibiting Enhancer of zeste 2 (EZH2) reduced senescence-associated secretory phenotype factors, suggesting therapeutic potential for tendinopathy regeneration.

Area Of Science

  • Cellular Biology
  • Epigenetics
  • Orthopedics

Background

  • Cellular senescence, a state of irreversible growth arrest, contributes to age-related tissue dysfunction.
  • Tendinopathies, characterized by chronic tendon pain and degeneration, lack effective regenerative treatments.
  • Enhancer of zeste 2 (EZH2) is a key epigenetic regulator implicated in various cellular processes.

Purpose Of The Study

  • To investigate the presence of senescent cells in human shoulder tendinopathy biopsies.
  • To correlate cellular senescence with Enhancer of zeste 2 (EZH2) expression.
  • To evaluate the therapeutic potential of targeting EZH2 and senescence in tendinopathy.

Main Methods

  • Analysis of tendon tissue biopsies from patients with chronic shoulder tendinopathies and controls.
  • Histological scoring for degeneration and assessment of senescence markers (p16, p19) and EZH2 expression.
  • Treatment of biopsies with senotherapeutic compounds and the selective EZH2 inhibitor EPZ-6438 to assess senescence-associated secretory phenotype (SASP).

Main Results

  • Senescence markers (p16, p19) and EZH2 expression were significantly elevated in tendinopathic tissues compared to controls.
  • Senescence marker expression positively correlated with the degree of tendon degeneration.
  • EZH2 inhibition with EPZ-6438 reduced the secretion of key SASP factors, including IL-6 and MMP3.

Conclusions

  • Cellular senescence accumulates in pathological tendon tissues and is linked to degeneration.
  • EZH2 expression is associated with tenocyte senescence in tendinopathies.
  • Targeting cellular senescence, potentially via EZH2 inhibition, offers a promising therapeutic strategy for chronic tendinopathies.

Related Concept Videos

Replicative Cell Senescence 02:15

3.6K

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...

Multipotency of Hematopoietic Stem Cells 01:19

3.0K

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...

Telomeres and Telomerase 02:41

23.0K

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...

Stem Cell Therapy for Tissue Regeneration 01:21

4.0K

Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...