Chondroyte desensitization to mechanical loading

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The overall goal of the proposed research program is to investigate the mechanisms responsible for the desensitization of cartilage cells to mechanical loading, and to develop methods to improve cellular sensitivity. The application of mechanical stimuli is a widely used method to enhance the growth of tissue engineered cartilage. However, as these cells rapidly desensitize to loading, the effectiveness of this approach is limited. While recent work has suggested that the potential cause of cellular desensitization to mechanical loading is related to intracellular calcium, the regulation of cellular calcium is complex as calcium is involved in several intercellular functions and processes. Through the study of intracellular calcium signaling during mechanical loading, it will be possible to identify the underlying cause of cellular desensitization and identify methods to improve cellular sensitivity. In addition, an alternative approach to mitigate the effects of cellular desensitization is through the modification of the applied loading protocols. Specifically, cellular sensitivity to mechanical stimuli can be altered by superimposing mechanical vibrations (noise) on the loading waveforms. This approach, termed “stochastic resonance”, has been successfully applied to improve sensitivity in other nonlinear biomedical systems including mechano-sensitive cells of the same lineage (e.g. osteocytes). While our preliminary studies have shown that this approach has the potential to limit loading-induced desensitization in chondrocytes, the extent of its effect as well as the underlying mechanisms responsible, have yet to be determined.