Skeletal aging is an elaborate process marked by environmental factors and biological mechanisms that result in reduced bone formation, stem cell exhaustion, and an increase in fat cells.
Although a decline in bone formation and loss of bone mass are common features of human aging, the molecular mechanisms mediating these effects have remained unclear.
Mesenchymal stem cells (MSCs) found in the bone marrow close to hematopoietic stem cells serve essential functions to allow bone marrow homeostasis. The majority of the bone cells are of mesenchymal cell origin. MSCs are also responsible for making and repairing skeletal tissues, such as cartilage, bone, and the fat found in the bone marrow.
The depletion of histone demethylase KDM4B significantly reduces osteogenic differentiation. It increases adipogenic differentiation (an increase of fat cells) of MSCs, limiting its ability to self-renew and differentiate into multiple cell types, including adipocytes, chondrocytes, and osteocytes.
While the epigenetic role of KDM4B in bone formation has already been established, the outcome of its absence was unknown.
Read the original publication of this study here: [ Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging ]
This study aimed to identify the consequence of KDM4B ablation in bone formation and bone loss processes.
Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging
Researchers from the UCLA School of Dentistry have identified the role of KDM4B in skeletal aging and bone loss, a finding that brings scientists closer to understanding the epigenetic mechanism that leads to osteoporosis.
Building on the established idea that KDM4B plays an epigenetic role in bone formation, the research team conducted a test to determine the effect of KDM4B deletion in the mouse model.
Researchers found that removing KDM4B resulted in adipogenesis, a mechanism where the mesenchymal stem cells create more fat cells instead of bone tissue, leading to bone loss over time.
The results further confirmed the critical role of KDM4B in osteogenic differentiation or mesenchymal stem cells’ ability to self-renew.
Also, it was found that a loss of KDM4B characterized stem cell senescence.
The accumulation of marrow fat in mice placed in a high-fat diet shows that environmental factors such as a high-fat diet may reduce bone quality and aggravate bone loss.
The results of this study suggest that reversing bone-fat imbalance and epigenetic rejuvenation might be new strategies for the prevention and treatment of skeletal aging and osteoporosis by activating KDM4B in mesenchymal stem cells.
Takeaways:
- Loss of KDM4B exacerbates bone-fat imbalance in skeletal aging and osteoporosis. Removal of KDM4B leads to adipogenesis or the increased production of fat cells from the stem cells.
- Stem cell senescence is characterized by a loss of KDM4B.
- KDM4B controls the ability of mesenchymal stem cells to self-renew.
You can read the original publication of this study here: [ Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging ]
- Basic biology of skeletal aging: role of stress response pathways
- Epigenetic Regulation of Bone Remodeling and Its Impacts in Osteoporosis
