Integrin Signaling and the Response of Osteocytes to Oscillatory Fluid Flow

+*Litzenberger, J B; *Tummala, P; *Jacobs, C R +*Veterans Administration Medical Center/Stanford University, Palo Alto, CA [email protected] INTRODUCTION Osteocytes are mechanosensitive cells in bone and are believed to be responsible for initiating and coordinating osteogenic and osteoclastic processes in vivo. Dynamic fluid flow has been shown to be a potent regulator of bone cell metabolism, but the molecular mechanism through which osteocytes sense mechanical stimuli is unknown [1,2]. Integrins, heterodimeric cell adhesion proteins, are ideal candidates for mechanosensitive molecules in bone due to their structural and catalytic capabilities. The aim of this study is to investigate the role of integrins in mechanotransduction in osteocytes. In response to mechanical stimuli, osteocytes coordinate a cellular response to load by directing effector cells to deposit or resorb bone [3,4]. Intracellular calcium ([Ca]i) mobilization and MAPK signaling in response to fluid shear stress are associated the deposition of bone matrix proteins in vitro [2]. Independent of calcium signaling, an increase in cyclooxygenase-2 transcription results in prostaglandin release from osteocytic cells and in bone formation in vivo [5–7]. It has also been shown that osteocytes have a loading-induced inhibitory effect on osteoclastogenesis, as measured by a decrease in the ratio of RANKL to OPG [8]. We hypothesize that inhibiting integrin signaling in osteocytic cells will decrease the production of molecular signals that drive osteogenic and osteoclastic processes in bone.