Sundar Srinivasan, Ph.D.
Department of Orhtopaedics & Sports Med (Orthopaedic Sciences Lab)
E-mail: sundars@u.wa...


TITLE:

"Exploring Bone Tissue Adaptation as a Bottom-Up Process via Experimental and Computational Approaches"


ABSTRACT:

Mechanical loading of the skeleton, as occurs during physical activity, is a critical determinant of bone structure and morphology.  Importantly, increased loading of the skeleton is anabolic (e.g., weight lifting, tennis) and can be used to augment bone mass and strength.  Given the promise of physical exercise, mechanical loading represents a noninvasive means to counteract increased skeletal fragility associated with aging and menopause.  However, the promise of physical exercise has remained unrealized, in part because the elderly are unable to comply with the types of vigorous exercise known to increase bone mass in the young.  Furthermore, aging degrades a number of cellular functions involved in bone mechanotransduction (or how cells perceive and initiate biochemical cascades in response to the stimulus).  In this seminar, I will present our research exploring mechanotransduction as a bottom-up adaptive process using a unique technique called agent-based modeling.  In an ongoing effort, we have developed a model of cellular signaling pathways activated acutely in bone cell networks by mechanical stimuli (order of mins).  Upon calibration against experimental data, the model simulated adaptation induced by a variety of mechanical stimuli and identified a therapy that, when implemented in vivo, rescued bone adaptation at senescence.  Furthermore, by examining how auto-regulation emerges following repeated loading and effectively de-sensitizes bone adaptation, we expect to determine when and how frequently to load bone in order to efficiently maximize adaptation.