News Release: Research , School of Medicine
Sep. 2, 2009
Bone-Building Hormone Acts Indirectly Through Immune Cells
Parathyroid hormone (PTH) controls the level of calcium in the blood through its effects on bone, kidney and intestinal cells.An important hormone that regulates bone formation requires immune cells to amplify its bone-building effects, researchers at Emory University School of Medicine have shown.
The results, published online this week by the journal Cell Metabolism, demonstrate how bone health is intertwined with the immune system. The research could help doctors design new treatments that strengthen bone.
Parathyroid hormone (PTH) controls the level of calcium in the blood through its effects on bone, kidney and intestinal cells. The drug teriparatide, an artificial version of human parathyroid hormone, was approved by the FDA in 2002 as a treatment for osteoporosis.
When administered once a day, PTH can stimulate bone formation. But if the body produces too much PTH -- a result of kidney failure or a tumor, for example -- that can lead to osteoporosis.
"This is a bit of a paradox, and how intermittent treatment works has remained a mystery," says Roberto Pacifici, MD, head of the division of endocrinology at Emory University School of Medicine.
Working with Pacifici, postdoctoral fellows Masakazu Terauchi and Jau-Yi Li have demonstrated that T cells, part of the immune system, provide an important link between PTH and osteoblasts, cells responsible for bone formation.
In mice that are genetically engineered to lack T cells, PTH treatment has little or no effect on bone density and bone formation, the authors show.
T cells also appear to contribute to the bone breakdown caused by continuous PTH treatment, because PTH stimulates them to produce a molecule called RANKL. RANKL in turn stimulates osteoclasts, which break down bone, the authors show.
PTH stimulates T cells to produce Wnt10b, a molecule already known to be important for bone growth and differentiation.
Wnt10b is part of a family of secreted Wnt molecules, which play critical roles in tissue differentiation throughout development. Scientists previously thought that the PTH-amplifying effects of Wnt came from osteoblasts acting on themselves, Pacifici says.
"It has been hard to reproduce the effects of PTH in vitro, and the idea that the Wnt came from different type of cells was not considered before," he says.
The results could help doctors design ways to enhance the effects of PTH or other treatments that strengthen bone, he says.
The research was supported by the National Institutes of Health.
Reference:
Terauchi et al. T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling. Cell Metabolism 10: 229-240, 2009.
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