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Overview

Leptin as a Regulator of Bone Formation in Microgravity

Principal Investigator:
Gerard Karsenty, M.D., Ph.D.

Organization:
Baylor College of Medicine

Dr. Gerard Karsenty’s research has shown that leptin, a signal molecule, negatively regulates bone formation. This research examines how this signaling process works and how to prevent leptin’s inhibitory effects on bone formation. This project may lead to the design of novel therapeutics enhancing bone formation.

NASA Taskbook Entry

Technical Summary

Original Aims
  1. To determine whether leptin controls bone mass by releasing a humoral substance following its binding to its hypothalamic receptor.
  2. To determine whether the sympathetic nervous system is involved in mediating leptin control of bone formation.
  3. To determine whether a naturally occurring soluble some of the leptin receptor can prevent leptin inhibitory action on bone formation.

Key Findings
Several key findings were made during the previous year of funding. These can be summarized as follows:

  • Leptin uses different pathways to control bone mass and body weight.
  • The concentration of leptin in blood is not a good indicator of its action on bone formation.
  • Neurons present in the hypothalamus and controlling bone formation have been identified.
  • The mediator coming out of these neurons and affecting bone formation is not present in blood.
  • Circulating leptin level controls bone mass.

Impact of Findings
These findings confirmed largely our working hypothesis that there is a brain-derived neuronal control of bone mass. They lead us to propose new experiments to identify the mediator relaying information form the brain to the bone cells.

In the coming year, we intend to use mutant mouse strains deficient in various neuromediators to identify the mediator of leptin action on bone mass. Once we have identified this mediator, we will generate an inhibitor of this mediation and we will use it in ovariectomized animals to determine whether it can be used to prevent the development of osteoporosis.

This project's funding ended in 2004