Noise-aided enhancement of nitric oxide production by bone cells in response to fluid shear stress

Abstract

The functional adaptation of bone to the demands of mechanical loading leads to efficient load bearing. This phenomenon is mediated by the activity of bone cells in response to loading-induced fluid flow in bone. Previously, we found that bone cells respond to fluid shear stress in a rate-dependent manner. However this response required an initial stress-kick to occur, suggesting that bone cells overcome a loading threshold to respond. This provides a basis for stochastic resonance to occur in bone as a non-linear biological system. Stochastic resonance is manifest in non-linear systems, whereby the response to a small periodic signal is enhanced by noise at an optimum level. It is possible that bone cell mechanosensitivity is enhanced by a noisy loading environment to take advantage of stresses occurring during exercise and in strenuous activities. We investigated whether the bone cell response to fluid shear stress is noise-aided. MC3T3-E1 osteoblastic cells were subjected to a small (below-threshold), periodic fluid shear stress stimulus (at 9 Hz, 0.12 Pa amplitude) superposed with Gaussian white noise of varying intensities using a parallel-plate flow chamber. Nitric oxide (NO) production was measured as the parameter for bone cell activation. We found that the response of bone cells to a small periodic fluid shear stress was non-monotonic reaching a maximum at a noise intensity of 0.32 mL/min. This finding supports the possibility that bone cell mechanosensitivity is enhanced by stochastic resonance. Bone cells might take advantage of noisy stress environments as in exercise or strenuous activities for bone functional adaptation to mechanical loading.