Speaker: Dr. Randall L. Duncan
Title: Cytomechanics: The Stress and Strain of Maintaining Bone
When: Friday, May 5, 2006
Where: 114 Spencer Lab, 12:00 PM Refreshments will be served
The mechanical environment is crucial to the function of numerous cell types from a
variety of tissues, including bone. Removal of physical stimulation, as in immobilization
or microgravity, results in significant loss of bone mass, while application of exogenous
mechanical loading can increase bone formation in the modeling skeleton. Various in
vitro loading techniques have been developed to study cellular responses and
mechanisms involved in the perception of mechanical stimuli by bone cells. While none
of these loading models completely replicate the stresses endured by bone, many
produce responses that are considered anabolic in osteoblasts. One of the principle
challenges in the study of mechanotransduction is combining the method of loading with
techniques designed to measure early cellular responses. For example, the
earliest recorded response of osteoblasts to a mechanical load is a rapid increase in
intracellular Ca2+ that occurs within seconds of the onset of the load. This increase is
dependent on both intracellular Ca2+ release and extracellular Ca2+ entry. To
determine the role of ion channels in mechanotransduction and changes in channel
kinetics in response to a mechanical stimulus, patch clamp techniques are used. These
techniques require exquisite stability to maintain the patch. Thus, the type of
mechanical stimulation used must be physiologically relevant, yet provide minimal
displacement of the cell. This is further complicated by the need to quantitate the forces
placed on the cell. We have shown that application of various types of mechanical
stimulation to osteoblasts activate mechanosensitive channels, L-type Ca2+
channels and outwardly rectifying K+ channels that act in synchrony to elicit an
increase in [Ca2+]i. This increase is responsible for initiation of a cascade of events
that, ultimately, result in bone formation.
ABOUT THE SPEAKER:
Dr. Randall L. Duncan is an Associate Professor of the department of Biological
Sciences with a joint appointment with the department of mechanical engineering at
University of Delaware.