Abstract: The skeleton is a dynamic organ system that has the ability to self-repair damage. The focus of this talk is the biological response that occurs when damage is created in a living bone. We use fatigue loading to induce a controlled crack (“stress fracture”) in the ulna of a rodent. This protocol causes an immediate loss of structural stiffness and strength that is proportional to the amount of fatigue damage. There are two distinct responses that follow. On the interior of the bone, where the crack formed, there is activation of targeted resorption by osteoclasts as the initial step in repairing the internal damage. On the surface, there is rapid deposition of new woven bone, i.e., the formation of a hard periosteal callus. The new woven bone greatly increases the cross-sectional area of the ulna and leads to recovery of structural stiffness and strength within 2 weeks. The molecular events that drive this surface repair process are a current focus. Numerous genes are activated soon after damage, including those associated with inflammation and bone regeneration. A critical component of this repair response appears to be an early increase in blood flow resulting from vasodilation, and also an increase in surface (periosteal) vascularity prior to bone deposition. The vasculature may serve as a template for new bone formation. One gene that appears to be turned on in vascular cells (and later in bone cells) soon after stress fracture is bone morphogenetic protein 2 (BMP-2). We are examining the requirement of BMP-2 in this process by creating mice which have targeted deletion of BMP-2 in vascular and bone cells.

Bio: Matthew Silva is a mechanical engineer who has worked on skeletal biomechanics his entire career. After receiving a BS (1982) and M.Eng. (1984) from Cornell University, he worked as a design engineer and analyst at the Hospital for Special Surgery in New York City. He returned to graduate school to focus on bone mechanics and in 1996 received his Ph.D. from Massachusetts Institute of Technology. Since 1996 he has been at Washington University, Saint Louis, with a primary appointment in Orthopaedic Surgery. He was promoted to Professor in 2009. He is Associate Director of the Musculoskeletal Research Center, a 62-member center devoted to advancing basic science and translational research related to osteoporosis, osteoarthritis and other skeletal maladies. His current research focus is bone mechanobiology, i.e., the study of how bone responds to mechanical stimuli ranging in intensity from mild to injurious.

~BME Faculty Host: Russell Main~

(via teleconference to SL165 at IUPUI)

***Coffee and juice will be provided at West Lafayette***