Previously, Dr. Ishii had discovered that the chemoattractant sphingosine-1-phosphate (S1P), which is associated with the trafficking of immune cells into and out of the lymph nodes, also caused immature osteoclasts to mobilize.
"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 migr
|Contact: Julie Wu|
NIH/National Institute of Allergy and Infectious Diseases