Bone undergoes continuous remodeling in response to mechanical loading. However, the underlying mechanisms by which bone cells respond to their changing mechanical environment, that is, strain in the load-bearing matrix or fluid flow through the canalicular network, are not well understood. It has been established in vitro that bone cells respond differently to substrate strain and fluid shear stress treatments. Uncovering the mechanical basis of these differences represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. To investigate this problem, we developed a biomechanical model of an adherent cell, to test the hypothesis that bone cells respond differently to 0.6 Pa fluid shear stress and 1,000 mu(epsilon) substrate strain stimulation because of qualitative and quantitative differences in the cellular deformation caused. Fluid shear stress loading conditions resulted in maximum displacements at the apical surface of the cell approximately 8 times higher than those due to strain at the cell-substrate interface and also caused higher stressing of all parts of the cell. Significantly, this shows that the deforming effects of fluid shear stress and strain on a cellular level are qualitatively different, which may provide a basis for explaining differences in bone cell responses to both stimuli as reported in several studies. Although our approach to modeling the morphology and complex physical environment of an adherent cell is certainly simplified, our results do show independent roles for fluid flow and strain as mechanical stimuli and highlight the importance of deformation on a cellular level in bone physiology.

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Short-term symptomatic relief is the only evidence-based benefit of corticosteroid injection of an osteoarthritic knee. Accurate intra-articular placement is not achieved in up to 20% of injections and varies considerably with the anatomical approach used. There is no evidence that a medial approach is more accurate. The incidence of serious infectious complications following knee joint injections ranges widely, and may be as high as 1 in 3,000 and potentially far higher in high-risk patients for whom specialist management is advised.

Nitric oxide (NO) released from mechanosensitive bone cells plays a key role in the adaptation of bone structure to its mechanical usage. Despite its importance in bone, the mechanisms involved in NO mechanotransduction at the cellular level remain unknown. Using combined atomic force microscopy and fluorescence microscopy, we report both stimulation and real-time monitoring of NO responses in single osteoblasts induced by application of quantified periodic indenting forces to the osteoblast membrane. Peak forces ranging from 17 to 50 nN stimulated three distinct NO responses in the indented osteoblasts: (1) a rapid and sustained diffusion of NO from the perinuclear region, (2) diffusion of NO from localized pools throughout the osteoblast, and (3) an initial increase and subsequent drop in intracellular NO. Force-indentation characteristics showed considerable interosteoblast variation in elasticity. NO responses were associated with application of force to more rigid membrane sites, suggesting cytoskeletal involvement in mechanotransduction. ß