Investigators identify chemical mediator that may direct bone homeostasis

New research indicates that a chemical mediator in the blood that is associated with immune cell migration may also be a key factor in bone metabolism.

Investigators say that the chemoattractant, sphingosine-1-phosphate, may provide a new target in the treatment and prevention of degenerative bone diseases.

Ronald Germain, MD, PhD, an immunologist at the National Institute of Allergy and Infectious Diseases (NIAID), conducted the research, which expands upon the work of Masaru Ishii, MD, PhD, a rheumatologist and visiting fellow from Osaka University in Japan. Ishii discovered that sphingosine-1-phosphate (S1P) caused the mobilization of immature osteoclasts.

The latest research conducted by Ishii, Germain and colleagues appears in Nature.

“Most current therapies for bone-degrading diseases target mature osteoclasts,” NIAID Director Anthony S. Fauci, MD, said in a press release. “Understanding how immature osteoclasts are recruited to the bone in the first place and targeting the signals that control that migration represents a potential new approach to treating and preventing debilitating joint and bone diseases.”

Using a novel imaging technique in live mice, the investigators discovered that immature osteoclasts migrated away from bone in response to S1P. An additional test comparing mice with S1P on their cell surfaces to those without S1P revealed that mice with S1P had denser bones.

The investigators also examined the effect of a synthetic S1P activator, FTY720, in a postmenopausal mouse model. They discovered that mice treated with FTY720 had greater bone density and showed fewer immature osteoclasts on their bones than untreated mice, according to the press release.

“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,” Germain said in the release.

Reference:
Ishii M, Egen JG, Klauschen F, et al. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature. Online edition posted Feb. 8, 2009.