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Mechanisms of Mechano-Transduction Within Osteoblasts

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Final rept. 1 Sep 1998-31 Aug 2001

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Mechanical stimulation is crucial to the homeostasis of adult bone density and mass. The hypothesis of this proposal is that bone cells sense their mechanical environment through specific cell surface receptors integrins that interact with specific extracellular matrix ECM proteins osteopontin, bone sialoprotein, and fibronectin that are the ligands for these receptors. We propose that the expression of these proteins is regulated in response to both cellular interactions with the ECM and mechanical stimulation. Thus, these proteins act like autocrine factors that modify cell behavior in response to changes in either matrix composition or mechanical deformation of the ECM itself. The proposed experiments will define how osteoblasts discriminate the molecular mechanisms by which mechanical signals mediate their actions through the cellular interactions of integrins with the ECM. A determination of the specific integrin isotypes that are involved in the mechano-signal transduction process will be made. The signal transduction systems that are responsible for mediating osteopontin, bone sialoprotein and fibronectin gene expression in response to mechanical stimulation, will be determined. Other experiments will examine how aspects of the mechanical stimuli, such as frequency, intensity or duration, effect cell response. Knowledge gained from understanding mechano-signal transduction will facilitate the development of appropriate clinical approaches to enhance the adaptive responses of skeletal tissue to mechanical stimulation.

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  • Anatomy and Physiology

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