Fluid flow in the osteocyte mechanical environment : a fluid-structure interaction approach

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid–structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity (3,000με compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities (∼60.5μ m/s ) and average maximum shear stresses (∼11 Pa ) surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology

Prostaglandin E2 is crucial in the response of podocytes to fluid flow shear stress

Podocytes play a key role in maintaining and modulating the filtration barrier of the glomerulus. Because of their location, podocytes are exposed to mechanical strain in the form of fluid flow shear stress (FFSS). Several human diseases are characterized by glomerular hyperfiltration, such as diabetes mellitus and hypertension. The response of podocytes to FFSS at physiological or pathological levels is not known. We exposed cultured podocytes to FFSS, and studied changes in actin cytoskeleton, prostaglandin E2 (PGE2) production and expression of cyclooxygenase-1 and–2 (COX-1, COX-2). FFSS caused a reduction in transversal F-actin stress filaments and the appearance of cortical actin network in the early recovery period. Cells exhibited a pattern similar to control state by 24 h following FFSS without significant loss of podocytes or apoptosis. FFSS caused increased levels of PGE2 as early as 30 min after onset of shear stress, levels that increased over time. PGE2 production by podocytes at post-2 h and post-24 h was also significantly increased compared to control cells (p < 0.039 and 0.012, respectively). Intracellular PGE2 synthesis and expression of COX-2 was increased at post-2 h following FFSS. The expression of COX-1 mRNA was unchanged. We conclude that podocytes are sensitive and responsive to FFSS, exhibiting morphological and physiological changes. We believe that PGE2 plays an important role in mechanoperception in podocytes

Exostoses of the Bony Pyramid of the Nose : A Review About an Adaptive Response to Mechanical Stimuli Exerted by In-Flight Oxygen Masks

This review addresses thickening of the bony pyramid of the nose, a condition that is caused by in-flight oxygen masks in otherwise healthy Royal Netherlands Air Force (RNLAF) F-16 pilots. The overlying skin may show temporary or permanent reddening, irritation, thickening and may become painful. Both in vitro and in vivo animal research has shown that mechanical stimuli are converted into a biochemical response through a process called mechanotransduction. Examination of the RNLAF F-16 pilots showed that the oxygen mask exerts pressure and friction on the nose. The biochemical response to chronic exposure to these stimuli results in the development of skin conditions and eventually exostoses of the bony pyramid of the nose. Painful skin conditions are most frequently observed, while the development of exostoses is rare. It lies at the extreme end of the spectrum of the pilots’ nasal conditions. The suboptimal fit of their work gear probably contributes to the pilots’ soft and bony tissue nasal conditions. Explaining the pathogenesis of the development of exostoses may aid in the development of preventive measures. Also, the obtained knowledge may be of use in similar occupational health issues that involve mechanical loading. Our conclusions are that areas containing osteocyte precursors and covered by a relatively thin cushioning layer are prone to develop a soft tissue and bony tissue response when they are chronically exposed to intermittently exerted, mechanical stimuli of sufficiently high magnitude. Modification of the suboptimally fitting oxygen mask–helmet assembly is needed to prevent symptoms associated with its use