In the first project, Avioli, co-investigator Roberto Civitelli, M.D., associate professor of medicine and assistant professor of cell biology and physiology, and research instructor Su Li Cheng, Ph.D., will study the influence of certain receptors on osteoblast movement, growth and other activities. The receptors called integrins allow osteoblasts to attach to the extracellular matrix, a supportive network surrounding bone cells. The investigators will determine how specific integrins influence osteoblast activity by serving as biological switches that turn on internal signals regulating cell behavior. Keith Hruska, M.D., Ira M. Lang Professor of Nephrology and associate professor of cell biology and physiology, will lead a second project to determine if integrins stimulate osteoblasts to build bone as a result of physical activity. Whenever a person takes a step or whacks a tennis ball with a racket, the physical movement and weight of the activity is picked up by the skeleton, which stimulates osteoblasts.
Osteoblasts also influence osteoclast function.
Stephen L. Gluck, M.D., professor of medicine and of cell biology and physiology, and Howard G. Welgus, M.D., professor of medicine, will investigate whether degradative enzymes secreted by osteoblasts and other bone cells tell the bone-degrading cells which sections of bone to work on. The metalloproteinase enzymes are thought to mark an area in need of remodeling by littering it with fragments of an extracellular matrix protein called collagen. While the influence of osteoblasts on osteoclast development and function has been established, researchers know little about whether the converse scenario occurs. They will examine soluble molecules called chemokines produced by osteoclasts, determine factors influencing their production and the effect of the chemokines on osteoblast development and function. A core laboratory directed by Leonard Rifas, research assistant professor of medicine, will act in a pivotal role by providing bone cell material essential to the studies and by providing support material for researchers' cell and molecular studies to analyze bone cell development and activity.