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.