Bone cells occupy fluid filled lacunae in the mineralized matrix and are interconnected by canaliculi. As bone is cyclically loaded, fluid flows in the lacunar-canalicular network from regions of high matrix strain to low matrix strain and back in an oscillatory fashion. Although it has been demonstrated that bone cells respond to steady and pulsatile fluid flow with a transient elevation in intracellular calcium concentration, increased release of paracrine factors, and increased gene transcription, our preliminary data indicate that these responses may be fundamentally different from those observed for oscillating flow. To date no experimental system has been designed to study responsiveness to physiologic oscillating fluid flow as a function of frequency and flow rate. To this end, the Principal Investigator and his co-investigators have developed a functioning oscillatory fluid flow exposure apparatus. This has allowed them to observe a frequency dependent intracellular calcium response to physiologic levels of oscillating fluid flow. The central hypothesis is that physiologic levels of oscillatory fluid flow provide an important mechanism of mechanotransduction, and furthermore shear stress level, frequency, time course, low level steady flow and cell dimensions modulate the cellular response. To test this hypothesis the investigators will apply combinations of shear stress, altering level and frequency, and measure cell signaling and metabolism. They are also interested in whether the intracellular calcium response to oscillating flow is followed by a refractory period as well as the possibility that oscillating and low level steady fluid are together synergistic. Finally studies are proposed to investigate the influence of cell dimension on response. The long-term goal is to understand how mechanical loading influences the behavior of bone.
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