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Role of angiogenic factors in bone loss induced by hindlimb unloading

Research project PX/7/LP/08 (Research action PX)

Persons :

Description :

In normal adults, bone formation is in equilibrium with bone resorption. Skeletal unloading in humans and rats, as seen during spaceflight, induces a decrease in bone formation and a transient increase in bone resorption resulting in bone loss and compromised bone mechanical properties. Several experimental data indicate that osteoblasts function inappropriately in microgravity. Understanding the underlying mechanisms of this process will certainly contribute to the prevention and treatment of space flight induced osteopenia but also to age-related osteoporosis.

The hypothesis tested in this project states that mechanical unloading, as during space flight, results in decreased blood flow in bone which on its turn affects the expression of angiogenic factors including vascular endothelial growth factor (VEGF) and possibly its homolog placental growth factor (PlGF). These angiogenic factors also affect osteoblast and osteoclast function.

A plausible pathway by which microgravity or skeletal unloading may be transduced into biochemical signals is related to changes in oxygen homeostasis in bone forming cells. Upon hindlimb unloading, blood flow declines and osteocytes become hypoxic and produce hypoxia inducible factor 1. This later factor is a strong stimulus of VEGF, a potent angiogenic factor. An attractive candidate for the pathological bone remodeling due to skeletal unloading is PlGF, a homolog of VEGF. This factor is especially involved in pathological conditions of angiogenesis and inflammation. We aimed to investigate the contribution of PlGF in bone loss induced by hindlimb unloading using mice deficient in PlGF. When a difference in bone loss between wild type and PlGF deficient mice is observed we will investigate whether this is due to an osteoblast or osteoclast phenotype, using techniques developed for other studies on bone metabolism and angiogenic factors.

Satellite(s) or flight opportunity(ies):

- Mice Tail Suspension (Ground Facility)

Field of research:

Life Science: Biology: Cell & Developmental Biology
Life Science: Human Physiology: Bone & Muscle Research

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