The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E 2 release in osteocytes and osteoblasts

Abstract

Fluid flowing through the bone porosity might be a primary stimulus for functional adaptation of bone. Osteoblasts, and osteocytes in particular, respond to fluid flow in vitro with enhanced nitric oxide (NO) and prostaglandin E 2 (PGE 2) release; both of these signaling molecules mediate mechanically-induced bone formation. Because the cell cytoskeleton is involved in signal transduction, we hypothesized that the pulsatile fluid flow-induced release of NO and PGE 2 in both osteoblastic and osteocytic cells involves the actin and microtubule cytoskeleton. In testing this hypothesis we found that fluid flow-induced NO response in osteoblasts was accompanied by parallel alignment of stress fibers, whereas PGE 2 response was related to fluid flow stimulation of focal adhesions formed after cytoskeletal disruption. Fluid flow-induced PGE 2 response in osteocytes was inhibited by cytoskeletal disruption, whereas in osteoblasts it was enhanced. These opposite PGE 2 responses are likely related to differences in cytoskeletal composition (osteocyte structure was more dependent on actin), but may occur via cytoskeletal modulation of shear/stretch-sensitive ion channels that are known to be dominant in osteocyte (and not osteoblast) response to mechanical loading.