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Novel Mechanism for targeting bone marrow adipocytes to prevent bone loss
Context: Recently, a research team from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has revealed that targeting estrogen-related receptor α (ESRRA) in adipocytes could be a potential therapeutic target for osteoporosis.
Bone marrow:
- It is the soft, spongy tissue rich in blood vessels located at the centre of most bones. It comes in two types: red and yellow.
- Red bone marrow contains blood stem cells that can develop into red blood cells, white blood cells, or platelets.
- Yellow bone marrow is primarily composed of fat and contains stem cells that can differentiate into cartilage, fat, or bone cells.
Adipocytes:
- Adipose tissue, also referred to as fat tissue or fatty tissue, is a type of connective tissue primarily composed of adipocytes, which are cells that store energy. It contains large lipid droplets surrounded by a structural network of fibres.
Novel Mechanism for Targeting Bone Marrow Adipocytes to Prevent Bone Loss:
- Bone Marrow Adipocytes (BMAds): Situated within the bone microenvironment, BMAds are close to bone cells, vascular structures, and hematopoietic tissues.
- Pathophysiological conditions can shift bone marrow stromal/stem cells (BMSCs) towards adipogenic progenitors at the expense of osteoprogenitors.
- Researchers explored the mechanisms underlying excessive BMAds in mediating cellular communication among bone-resident cells.
- Key Discovery: The absence of ESRRA in adipocytes alters the expression of secreted factors that affect BMSCs fate determination and vascular endothelial cell angiogenesis.Targeting ESRRA in adipocytes could serve as a therapeutic target for osteoporosis.
- Study published in Nature Communications showed that adipocyte-specific ESRRA knockout rescues bone loss, restores type H vessels, and inhibits marrow adiposity in mice induced by ovariectomy (OVX) or diet-induced obesity (DIO).
- Pharmacological Inhibition: Inhibition of ESRRA significantly restricts marrow adipose tissue expansion and promotes bone formation in obese mice, preventing bone loss and high marrow adiposity.
- Therapeutic Potential: This study provides a new method for treating bone disorders, especially in clinical conditions associated with high marrow adiposity, by targeting ESRRA.
What is osteoporosis?
- It is a condition that causes bones to become weak and thin, reducing their density.
- Individuals with osteoporosis have bones that are much more fragile, less denser and weaker than normal,
- making them susceptible to bone fractures even from minor impacts or stresses.
- With age, bones naturally lose density and their ability to regenerate.
