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Research Provides Clues to How the Skull Grows in Response to PressureMarch 30, 1999 Key elements that cause the skull to grow in response to pressure have been found by researchers at the Medical College of Georgia. This information helps explain how a healthy baby's skull grows in response to his increasing brain size and why a hydrocephalic baby's skull grows dramatically in response to abnormally high pressures inside. "It is known that pressure applied to the skull affects skull shape," said Dr. James L. Borke, MCG physiologist. "What is not known is how pressure is transferred to bone growth." To answer that question, Dr. Borke and Dr. Jack Yu, craniofacial surgeon at the MCG Children's Medical Center, have focused on the suture sites in the still-growing skull of newborn rats. A baby has many of these sutures, which are sites of bone growth between solid pieces of skull; a baby's 'soft spots' are where sutures meet. Growth of the skull in the first few years of life is crucial to normal development and even survival. In the first six months of life, brain growth is rapid and continues at a decelerating pace until about age 3. "If you don't allow the volume (of the skull) to go up, the pressure inside the head is going to shoot up so high that it is incompatible with life," Dr. Yu said. After brain growth ceases, the skull eventually becomes a solid, protective mass of bone. In the laboratory, the MCG researchers have documented that bone cells closest to the sutures stretch and become permeable when placed under tension. Fibroblast growth factor 2 is one of the first escapees through the newfound permeability and it triggers the series of events that allows the host cells as well as neighboring bone cells to grow, Dr. Yu said. The researchers also have identified two proteins that play a role in bone's growth response to tension. Alpha smooth muscle actin tells the cell's internal mechanisms that the cell membrane has been stretched, Dr. Borke said. Alpha smooth muscle actin functions as part of the cell's skeleton, so when the cell is stretched, the skeleton moves, activating chemical reactions responsible for communicating the stretch, he said. A second protein, connexin 43, helps nearby cells, which aren't directly stretched, learn what's going on around them. Connexin 43 forms gap junctions, tiny bridges between cells that are so small that most cellular components can't travel across. But calcium and substances called second messengers can travel across gap junctions, communicate to the adjoining cell that stretching is taking place and tell the cells to respond by growing. "The suture may respond to stretching by communicating with the first bone cells on either side, then those bone cells are connected by gap junctions to other nearby bone cells so they can form this multi-cellular response," Dr. Borke said. "The whole (cellular) neighborhood can respond to the stretch." "Form follows function," explained Dr. Yu. "Wherever cells gets stretched the most, they leak more of the things that make them grow. It's just a perfect, beautifully self-stabilizing model." Drs. Borke and Yu have shown in the laboratory that when tension is put on a suture, the two structural proteins and fibroblast growth factor 2 are up-regulated, which means they increase in number after bone cells are stretched. Dr. Borke noted that the three substances normally are present and play a role in bone growth. It's only when pressure is abnormal, such as in hydrocephaly B when too much cerebrospinal fluid accumulates in the skull B that abnormal bone growth results. Conversely, if there is decreased pressure inside the skull, the skull may not grow big enough. For example, if a shunt placed in a hydrocephalic baby to reduce excessive intracranial pressure removes too much fluid, the skull may not grow large enough for the fully developed brain. Premature fusion seems to occur spontaneously in other children, resulting in a range of scenarios from a misshapen head to a life-threatening condition. Dr. Yu, director of the Craniofacial Center at the MCG Children's Medical Center, regularly reshapes the skulls of these children in the operating room. The growth mechanism applies in other areas of the body as well. For example, it's how braces work to move teeth around in the mouth; braces act as an artificial force to change the way bone grows, said Dr. Borke, who has published studies documenting the up-regulation of connexin 43 in response to tooth movement. Or, in a person born with a jaw that is too short, Dr. Yu knows that if he applies a device to stretch the mandible, eventually more bone will grow. Now he and Dr. Borke have information about how growth occurs and are working to fine-tune their model and identify all the steps involved. The researchers hope that by understanding the science of how growth occurs, better intervention measures can be identified for when the growth goes awry. |
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Copyright 2004 |
MCG Craniofacial Center August 06, 2004 |