Bone stuff in the Economist

Skeleton keys

Aug 9th 2007, from The Economist print edition

How the body puts flesh on its bones depends on the bones themselves

ANATOMY used to be a straightforward business. The body was divided up neatly into organs and systems that each had well-defined tasks. Indeed, for the past 150 years “Gray's Anatomy”—the 1858 textbook that defines the genre—has dissected the body along these thematic lines: nervous, circulatory, digestive and so on.

But the lines are becoming increasingly blurred. Gerard Karsenty of Columbia University and his colleagues report another such smudging in Cell this week. They have found that people's bones do much more than just provide scaffolding for their floppy innards. They have caught the skeleton behaving as part of the endocrine system, the scheme by which the body uses hormones to signal its needs.

It has long been known that the human skeleton constantly constructs and destroys cells, according to the stresses that its bones experience. Some cells produced in bone, called osteoblasts, build bone where it is needed. Another set of cells, osteoclasts, destroy it where it is deemed no longer necessary.

The researchers decided to examine the role of osteocalcin, a protein produced by osteoblasts. To do so, they used some mice that had been bred to lack the gene that instructs the body to make osteocalcin. The rodents were rather rotund, because osteocalcin helps regulate the cells that produce insulin in the pancreas and release it into the bloodstream. Insulin, in turn, controls the levels of sugar in the bloodstream by directing how much of it is taken up by the liver. Mice that produced no osteocalcin lacked this hormonal weight-control mechanism.

Moreover osteocalcin also sends signals to fat cells directly, causing them to release another hormone called adiponectin that makes the body more sensitive to the effects of insulin. This dual control on how the body deals with blood sugar is ultimately what determines weight gain and whether or not fat is burned.

Because osteocalcin is produced only by osteoblasts yet acts on cells far away in the pancreas, the researchers concluded that bone is part of the endocrine system, and that it may hold a key to both obesity and diabetes. Indeed, when Dr Karsenty fed his mice traces of osteocalcin, their blood sugar levels dropped and their insulin production increased. The researchers hope that the effects will be the same in people. The team is trying to find this out, with a view to developing a treatment for those with diabetes.

More secrets may be revealed by research into the skeleton's more acknowledged role of scaffolding. The osteoblasts are the foremen of bone construction, and they appear to respond to the flow of fluid in the tiny channels within bone. When bones have to help lift a weight, the fluid gets sloshed about, leading to the proliferation of osteoblasts in the areas under the most stress. But just how the bones sense this flow of fluid has been an open question, at least until now.

Christopher Jacobs, of Stanford University, and his colleagues, reporting last week in the Proceedings of the National Academy of Sciences, have identified the sensors as hair-like protrusions called primary cilia. These are found on the surface of many of the body's cells, and sway to and fro in moving fluid. When they were removed, Dr Jacobs and his colleagues found that no osteoblasts grew nearby. The finding could eventually prove useful in the treatment of osteoporosis, which is caused by overactive osteoclasts and underactive osteoblasts.

Three years ago “Gray's Anatomy” was reorganised according to the regions of the body rather than the functions of the systems. That bones continue to blur the boundaries of functional anatomy means that the classical textbook may yet see further revisions.