Osteoblastic cells have refractory periods for fluid-flow-induced intracellular calcium oscillations for short bouts of flow and display multiple low-magnitude oscillations during long-term flow

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Partitioning a daily mechanical stimulus into discrete loading bouts enhances bone formation in rat tibiae (J. Bone Mineral Res. 15(8) (2000) 1596). We hypothesized that a refractory period exists in primary rat osteoblastic cells, during which fluid-flow-induced [Ca2+]i oscillations are insensitive to additional short bouts (2min) of fluid flow. Because the frequency of [Ca2+]i oscillations is believed to be important for regulating cellular activity and long-term fluid flow alters gene expression in bone cells, we also hypothesized that long-term (15min) oscillating fluid flow produces multiple [Ca2+]i oscillations in osteoblastic cells. Primary osteoblastic cells from rat long bones were exposed to 2min of oscillating fluid flow that produced shear stresses of 2Pa at 2Hz. After a rest period of 5, 30, 60, 300, 600, 900, 1800, or 2700s, the cells were exposed to a second 2-min bout of flow. A 600s rest period was required to recover the percentage of cells responding to fluid flow and a 900s rest period was required to recover the [Ca2+]i oscillation magnitude. The magnitude and shape of the two [Ca2+]i oscillations were strikingly similar for individual cells after a 900s rest period. During 15min of continuous oscillating flow, some individual cells displayed between 1 and 9 oscillations subsequent to the initial [Ca2+]i oscillation. However, only 54% of the cells that responded initially displayed subsequent [Ca2+]i oscillations during long-term flow and the magnitude of the subsequent oscillations was only 28% of the initial response. © 2002 Elsevier Science Ltd. All rights reserved.

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Journal of Biomechanics