Sci. Aging Knowl. Environ., 18 February 2004
Vol. 2004, Issue 7, p. nf19
[DOI: 10.1126/sageke.2004.7.nf19]


Augmenting With Amylin

Hormone slows bone breakdown

Mary Beckman

Like a retaining wall that protects a beach house from the pounding ocean, a protein called amylin keeps bones strong by preventing their disintegration, new research shows. The results suggest a novel potential therapy against osteoporosis.

Healthy bones maintain a balance between cells called osteoclasts that break down old bone and cells called osteoblasts that replace it. The balance of demolition and construction in bones of the elderly and people with certain bone-thinning diseases goes awry: Osteoclasts rev up or osteoblasts slow down. In both cases, more razing than raising produces a delicate skeleton. Researchers have been identifying the molecular workers in the bone construction and demolition crews. The hormone amylin, for example, dampens bone breakdown by osteoclasts in test tubes. But researchers weren't sure how the hormone influenced bone in animals.

To address that question, Dacquin and colleagues generated mice that lacked both copies of the amylin gene. The bones of these otherwise healthy animals were about 30% thinner than normal. To determine whether the deficit resulted from lazy osteoblasts, the researchers injected a chemical that growing bone incorporates. Normal and amylin-deficient mice harbored the same amounts of the chemical in their bones, suggesting similar degrees of growth. Then the researchers measured byproducts of bone breakdown, which reflect osteoclast action. Rodents lacking amylin had about 50% to 100% more than the control animals did, indicating that the hormone normally hinders osteoclasts.

The scientists then investigated how amylin foils the skeleton-whittling cells. Researchers can coax cultured bone marrow cells first into infant osteoclasts and then into mature osteoclasts. The more amylin the scientists added to such a culture, the fewer mature osteoclasts arose. However, the number of immature destroyers remained constant, indicating that amylin prevents osteoclasts from realizing their full potential.

Hormones control cellular activities by docking to a protein receptor on the cell surface. Previous work revealed that amylin binds to a protein called the calcitonin receptor on osteoclasts--at least when the hormone is present at very high concentrations. But earlier experiments yielded perplexing results: Mice lacking the calcitonin receptor had bulky skeletons, which does not mesh with an antiosteoclast role for the protein. To nail down whether amylin uses the calcitonin receptor to thwart osteoclasts, the researchers created mice that lacked either one calcitonin receptor gene or one amylin gene. They then measured bone thickness and osteoblast and osteoclast activity. Rodents missing the receptor gene had thick bones due to extra osteoblast labor, confirming previous results, whereas mice lacking the amylin gene had thin bones due to extra demolition by osteoclasts. These observations indicate that the hormone does not engage the calcitonin receptor to encumber osteoclasts.

"The home run about this paper is the amylin story," says osteoclast biologist Steven Teitelbaum of Washington University in St. Louis, Missouri. "It's the first time [researchers] have really nailed" amylin's role in bone reconstruction. Because it prevents bone thinning, amylin is potentially useful in the fight against osteoporosis, he says. Perhaps the hormone will protect our own foundations from the waves of aging.

February 18, 2004
  1. R. Dacquin et al., Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J. Cell. Biol. 164, 509-514 (2004). [Abstract] [Full Text][Abstract/Free Full Text]
Citation: M. Beckman, Augmenting With Amylin. Sci. Aging Knowl. Environ. 2004 (7), nf19 (2004).

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