Related Experiment Video

Updated: Nov 19, 2025

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

34.4K

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in

Chao Xia1, Tianyuan Jiang1, Yonghui Wang1

  • 1Department of Geriatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Frontiers in Endocrinology
|January 28, 2021
PubMed

Insights

The p53 protein promotes cellular senescence and inhibits bone formation in mesenchymal stem cells (MSCs) by upregulating miR-145a, which targets Cbfb. This p53/miR-145a/Cbfb pathway offers potential therapeutic targets for osteoporosis.

Area of Science:

  • Biomedical Science
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Senescent bone marrow mesenchymal stem cells (MSCs) exhibit impaired osteogenic differentiation.
  • p53 is a known regulator of cellular senescence and a negative factor in bone formation.
  • The precise role of p53 in MSC senescence and differentiation requires further elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying p53's function in MSC senescence and osteogenic differentiation.
  • To explore the relationship between p53, miR-145a, and core binding factor beta (Cbfb) in MSCs.

Main Methods:

  • Induction of MSC senescence and osteogenic differentiation using H2O2 and BMP9, respectively.
  • Analysis of p53 and miR-145a expression levels.
  • Overexpression of miR-145a in MSCs.
  • Identification of Cbfb as a target of miR-145a.
  • Restoration of Cbfb expression to assess rescue effects.

Main Results:

  • p53 expression was upregulated during both MSC senescence and osteogenic differentiation.
  • miR-145a expression was significantly increased, induced by p53.
  • Overexpression of miR-145a promoted MSC senescence and inhibited osteogenic differentiation.
  • p53-induced miR-145a inhibited osteogenic differentiation by targeting Cbfb.
  • Restoring Cbfb expression reversed the inhibitory effects of miR-145a.

Conclusions:

  • The p53/miR-145a axis promotes MSC senescence and inhibits osteogenesis.
  • The newly identified p53/miR-145a/Cbfb axis is crucial for osteogenic differentiation.
  • This axis presents potential therapeutic targets for treating osteoporosis.
Keywords:
Cbfbmesenchymal stem cellsmicroRNAsosteogenic differentiationp53senescence

More Related Videos

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.4K
Induction and Validation of Cellular Senescence in Primary Human Cells08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

17.6K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.5K
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...
5.2K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.9K
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...
4.1K