A major goal of the program project is to determine osteocyte function in response to mechanical loading. Inorder to accomplish this goal it will be necessary to relate osteocyte deformation and/or strain in bone tissueto the expression and function of different molecules expressed by osteocytes in response to mechanicalloading. The overall support aim of this research core laboratory is to provide the mechanical loadinginstrumentation and define the loading protocols that will be applied in-vitro and in-vivo throughout theprogram project. Well-defined in-vitro, ex-vivo and in-vivo mechanical loading systems are of paramountimportance in conducting the work proposed in the individual projects. Although the precise nature of themechanical environment of osteocytes in-vivo is not known, the protocols described herein are generallyaccepted in the scientific community. This core will provide support to conduct in-vivo and in-vitro loading ofbones and bone cells, as well as the capability to image cells in-vitro and ex-vivo during application ofmechanical stimuli enabling the quantification of individual cell deformations. In addition, this core will be aresearch core where important questions regarding cell deformation in response to mechanical stimulationwill be investigated. Understanding the physical deformation of osteocytes due to different mechanicalstimulation will provide needed insight into differences observed in cell response. Our preliminary datasuggest that the hypothesis that bone cells do not respond to bone matrix strain may be incorrect. We haveshown that local peri-lacunar bone matrix strain can be up to 20,000 microstrain, an order of magnitudegreater than in-vivo bone surface strains measured using a strain gage and on average is 4,000-7,000microstrain when macroscopic strains of 2,000 microstrain are applied to bone. We have shown that in-vitroosteocyte cell deformation due to this level of shear stress can be between approximately 5,000 and 50,000microstrain with a concomitant biological response measured such as an increase in PGE2 production. Theresearch goals of this core are to quantify osteocyte deformation in-vitro resulting from both fluid flowgenerated shear stress and substrate stretching. Furthermore, to extend our current research findings, wewill measure osteocyte deformation ex vivo in mice long bones due to globally applied structural bendingloads. We will also begin to characterize the osteocyte microenvironment, which is integral in transmittingglobal structural loads and deformations to the osteocyte, by atomic force microscopy, nanoindentation, andDirect Raman imaging.
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