Functional and structural characterization of osteocytic MLO-Y4 cell proteins encoded by genes differentially expressed in response to mechanical signals in vitro

Abstract

Abstract The anabolic response of bone to mechanical load is partially the result of osteocyte response to fluid flow-induced shear stress. Understanding signaling pathways activated in osteocytes exposed to fluid flow could identify novel signaling pathways involved in the response of bone to mechanical load. Bioinformatics allows for a unique perspective and provides key first steps in understanding these signaling pathways. We examined proteins encoded by genes differentially expressed in response to fluid flow in murine osteocytic MLO-Y4 cells. We considered structural and functional characteristics including putative intrinsic disorder, evolutionary conservation, interconnectedness in protein-protein interaction networks, and cellular localization. Our analysis suggests that proteins encoded by fluid flow activated genes have lower than expected conservation, are depleted in intrinsic disorder, maintain typical levels of connectivity for the murine proteome, and are found in the cytoplasm and extracellular space. Pathway analyses reveal that these proteins are associated with cellular response to stress, chemokine and cytokine activity, enzyme binding, and osteoclast differentiation. The lower than expected disorder of proteins encoded by flow activated genes suggests they are relatively specialized.