"Because immature osteoclasts come from the same parent stem cell that gives rise to specific white blood cells already shown to respond to S1P," comments Dr. Ishii, "it seemed plausible that S1P could play a role in osteoclast migration."

Once at NIAID, Dr. Ishii worked with Dr. Germain's group to determine if S1P controlled immature osteoclast migration in live mice. Using a unique imaging technique, the researchers could see immature osteoclasts migrating away from the bones of the mice in response to S1P in the blood.


To confirm that S1P plays a direct role in bone metabolism, the research team compared the bone density in mice having the S1P receptor on their cells' surfaces with that of mice lacking the S1P receptor. They found that mice with functional S1P receptors had denser bones than mice lacking functional S1P receptors.

The researchers also tested a mouse model of postmenopausal osteoporosis to see if adding a synthetic S1P activator, known as FTY720, could help preserve bone. Postmenopausal mice given FTY720 had fewer immature osteoclasts on their bones and greater bone density when compared with untreated postmenopausal mice.

According to Dr. Ishii, these findings, combined with previous data, indicate that it may be possible to use combined therapies that target immature osteoclast migration and mature osteoclast function to treat and prevent bone-resorptive disorders.

"Observing that the S1P pathway plays a role in osteoclast migration is a good demonstration of 'osteoimmunology,' where the research disciplines of immunology and bone metabolism intersect," notes Dr. Germain.

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.Reference: M. Ishii et al. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature. DOI: 10.1038/nature07713.3d (2009).

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