Osteocytes elaborate an extensive mechanosensory network in bone matrix and communicate intercellularly via gap junctions established at dendrite termini. We developed a method to measure osteocyte dendritogenesis in vitro using a modified transwell assay and determined that the lipid growth factor lysophosphatidic acid (LPA) is a potent stimulator of dendrite outgrowth in MLO-Y4 osteocytes. The stimulatory effects were dose-dependent with maximal outgrowth observed within a physiological range of LPA. LPA-treated osteocytes exhibited distinct rearrangements of the actin cytoskeleton and a more stellate morphology than control cells. LPA also promoted osteocyte chemotaxis, suggesting a shared molecular mechanism between dendrite outgrowth and cell motility. The LPA-induced increase in dendrite formation was blocked by the specific LPA-receptor antagonist Ki16425 and by pertussis toxin. Bone cells in vivo encounter platelet-derived LPA in regions of bone damage, and we postulate that this lipid factor is important for re-establishing osteocyte connectivity during fracture repair. (c) 2007 Elsevier Inc. All rights reserved.