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How Growth Shapes Your Skeleton Before You're Even Born

Jay Henderson
Department of Mechanical Engineering
Stanford University
December 2001

I'm interested in understanding how and why the human skeleton grows the way it does. In particular, my research looks at how the interaction of growing tissues helps our skeletons end up the right size and shape. Unlike previous investigations of this topic, which tended to be purely biological, my approach combines biological and engineering techniques. The engineering approach adds insights into how normal pulling and pushing on bones during the growth process affects their shape. My hope is that this research will lead to a more complete understanding of how our bones grow normally so that we can be more successful at correcting skeletal problems due to injury or disease.

How does the human skeleton achieve its final shape? This question has long been a source of interest. A tremendous amount of biology and genetics research has sought to understand the process by which skeletal shape is created in the embryo. This process is called skeletal morphogenesis. While these investigations have revealed many of the biochemical signals involved during skeletal morphogenesis, biological research of this sort has tended to overlook other factors at work, such as biomechanical factors. My research focuses on one of these factors: growth-induced stresses. I'm interested in growth-induced stresses because previous research has indirectly shown the existence of growth-induced stresses, but no one has ever examined how growth-induced stresses influence development.

So what are growth-induced stresses? Very early in embryonic development skeletal tissues grow at different rates. Because the tissues grow at different rates, they pull and push on each other, creating forces between the tissues. These forces are called growth-induced stresses, because they create stress in the tissue as a result of tissue growth. These growth-induced stresses stimulate developing skeletal cells. It has long been known that cells of the body can react to mechanical stimulation - that is, pushing or pulling on the cells. We make use of this fact every day with our sense of touch, which transforms a mechanical stimulation of the skin into a signal the brain interprets as touch. Cells can respond to mechanical stimulation in this and many other ways. Previous research has shown that cells in the adult skeleton respond to mechanical stimulation produced during everyday life. For example, every time you walk, swim, or do any other activity, muscle contraction creates forces in your bones. Over time, cells in your bones respond to these forces by adjusting the density of your bones, so that your skeleton is strong enough to support the forces imposed upon it.

Previous research in my laboratory has investigated the ways mechanical stimulation affects bone growth during adolescence and bone changes during adult life. This has been accomplished by applying biomechanical engineering approaches to understanding the growth of bones. I am continuing this type of research but I am focusing on a much earlier stage of skeletal development. My research will determine the ways in which mechanical stimulation produced by growth-induced stresses influence skeletal tissue growth and affect skeletal morphogenesis. Because previous research of skeletal morphogenesis has often overlooked mechanical stimuli, my research will break new ground by integrating biological knowledge with biomechanical approaches. This integrated approach will create a more complete understanding of the many complex components of skeletal morphogenesis. To accomplish these goals I will combine computer modeling with laboratory experiments on skeletal tissues.

By better understanding normal skeletal growth, we will also gain insight into skeletal injury or disease. For instance, this research could influence the field of tissue engineering. Tissue engineering, which seeks to grow new tissue to replace damaged or diseased tissue, has focused primarily on the chemical requirements of growing tissues. Once we understand what mechanical stimuli result from growth-induced stresses during normal development, we can apply similar stimuli to engineered tissues and have a better chance of helping those suffering from skeletal injuries, diseases like arthritis, or improperly formed skeletons.