Related Experiment Video

Updated: Jan 27, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

35.0K

Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis

Xiaoqing Ren1, Boqiang Hu2, Moshi Song3

  • 1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Cell Reports
|March 28, 2019
PubMed

Insights

Chromobox 4 (CBX4) protein prevents human mesenchymal stem cell (hMSC) aging by maintaining nucleolar homeostasis. Lower CBX4 levels accelerate senescence, while its overexpression alleviates aging and osteoarthritis in mice.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Stem Cell Biology

Background:

  • Polycomb repressive complex 1 (PRC1) component CBX4 is crucial for cell identity and organ development via gene silencing.
  • The role of CBX4 in human stem cell homeostasis, particularly in aging, is not well understood.

Purpose of the Study:

  • To investigate the role of CBX4 in human mesenchymal stem cell (hMSC) aging.
  • To elucidate the mechanisms by which CBX4 influences stem cell homeostasis and senescence.

Main Methods:

  • Analysis of CBX4 protein levels in aged hMSCs.
  • CBX4 knockout and overexpression studies in hMSCs.
  • Assessment of nucleolar homeostasis, ribosome biogenesis, and protein translation.
  • Evaluation of cellular senescence markers.
  • In vivo studies using a mouse model of osteoarthritis.

Main Results:

  • CBX4 protein is downregulated in aged hMSCs.
  • CBX4 knockout leads to destabilized nucleolar heterochromatin, increased ribosome biogenesis, enhanced protein translation, and accelerated cellular senescence.
  • CBX4 recruits fibrillarin (FBL) and KRAB-associated protein 1 (KAP1) to nucleolar rDNA, limiting rRNA expression.
  • CBX4 overexpression alleviates hMSC aging and reduces osteoarthritis development in mice.

Conclusions:

  • CBX4 counteracts hMSC aging by maintaining nucleolar homeostasis.
  • CBX4's role in regulating rRNA expression is critical for preventing cellular senescence.
  • CBX4 represents a potential therapeutic target for aging-associated disorders like osteoarthritis.
Keywords:
CBX4CRISPR/Cas9agingepigeneticsgene editingheterochromatinnucleolusosteoarthritisrDNAstem cell

More Related Videos

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry09:38

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

Published on: June 26, 2019

8.6K
Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry14:01

Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry

Published on: September 13, 2022

5.7K

Related Concept Videos

What is Homeostasis?01:16

What is Homeostasis?

Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, from body temperature to blood pressure to levels of certain nutrients. A set point is the physiological value around which the normal range fluctuates. A normal range is a restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F).
53.4K
pH Homeostasis01:31

pH Homeostasis

Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory...
18.4K
Skeleton and Calcium Homeostasis01:21

Skeleton and Calcium Homeostasis

Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
5.9K
Replicative Cell Senescence02:15

Replicative Cell Senescence

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...
4.3K
Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.7K
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
4.0K