Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis

Area of Science:

• Skeletal Biology
• Vascular Biology
• Endocrinology

Background:

• Synthetic glucocorticoids (GCs) are crucial for treating pediatric inflammatory and autoimmune diseases.
• GCs negatively impact skeletal development, particularly bone angiogenesis, but mechanisms are poorly understood.
• Understanding GC effects on growing bone is vital for mitigating adverse skeletal outcomes.

Purpose of the Study:

• To elucidate the mechanisms by which GCs impair angiogenesis in the growing skeleton.
• To investigate the role of endothelial cell senescence in GC-induced skeletal abnormalities.
• To identify molecular targets for preventing GC-related bone growth inhibition.

Main Methods:

• Utilized young mouse models to study the effects of GC treatment on long bone metaphysis.
• Assessed vascular endothelial cell senescence, bone angiogenesis, and osteogenesis.
• Investigated the role of angiogenin (ANG) and its interaction with plexin-B2 (PLXNB2) in endothelial cell function.

Main Results:

• GC treatment induced vascular endothelial cell senescence in the bone metaphysis.
• Inhibition of endothelial cell senescence rescued GC-impaired bone angiogenesis and osteogenesis.
• Osteoclast-secreted angiogenin (ANG) protects vascular cells from senescence via the PLXNB2/rRNA pathway.
• GCs suppress osteoclast formation, reducing ANG production and leading to endothelial cell senescence.

Conclusions:

• Metaphyseal blood vessel senescence is a key mediator of GC adverse effects on the growing skeleton.
• The angiogenin/plexin-B2 (ANG/PLXNB2) axis is crucial for osteoclast-vascular communication in skeletal angiogenesis.
• Targeting the ANG/PLXNB2 pathway may offer therapeutic strategies to prevent GC-induced skeletal damage.