The foot bones of the jerboa are hard to miss. Longer than the animal’s arm, they help the bipedal desert rodent hop quickly away from predators. Now, they have also helped scientists better understand how bones grow to the right length. The finding helps explain some of the factors that affect the shape of skeletons, and they could eventually help to treat bone growth defects.
A growing bone lengthens when cells in its so-called growth plate, a region at the ends of growing bones, multiply and expand. The cells, called chondrocytes, form the cartilage that provides a scaffold for the mature calcified bone that later grows on top of them. Scientists knew that the size of the chondrocytes — not only their number — helped fix how much and how quickly a bone grows. But exactly what drives that cell size growth is a mystery.
To observe the changes that mouse chondrocytes undergo in the growth plate, developmental geneticist Kimberly Cooper and physicist Seungeun Oh of Harvard Medical School and their colleagues used diffraction phase microscopy, a technique that allowed them to quantify the size and density of living cells. In a paper published online last week in Nature, they reported that the cells in a growing mouse hind leg seem to go through three distinct phases. First, the cells roughly triple their volume while keeping their density relatively constant. In the second phase, cells swell dramatically, quadrupling their volume while their contents become much more dilute. In the third phase, the cells double their size again, but their density stays about the same.
When they compared fast- and slow-growing bones in the same animal, the researchers found that in slower-growing bones of the foreleg, cells went through phase one but stopped growing partway through phase two.
Further studies showed that when the gene that codes for insulin-like growth factor 1 (a hormone known to influence growth and metabolism) is disabled specifically in mouse hind legs, chondrocyte growth stops after phase two. That result suggests, Cooper says, that the gene might play a key role in determining how long different bones grow-and might provide clues to drugs that could help treat bone growth defects.
“It’s a very interesting new twist to a very old question of how bones grow," says Cornelia Farnum, an anatomist and professor emeritus at Cornell University.
Knowing how bones achieve the right length and shape could eventually help doctors treat bone growth defects.