Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes

• Published in: American journal of physiology: endocrinology and metabolism 1999-01, Vol.276 (1), p.E171
• Main Authors: Ajubi, N. E, Klein-Nulend, J, Alblas, M. J, Burger, E. H, Nijweide, P. J
• Format: Article
• Language: English
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.1999.276.1.e171

1  Department of Oral Cell Biology, ACTA-Vrije Universiteit, 1081 BT Amsterdam, The Netherlands; and 2  Department of Molecular Cell Biology, Leiden University Medical Centre, 2301 CD Leiden, The Netherlands To maintain its structural competence, the skeleton adapts to changes in its mechanical environment. Osteocytes are generally considered the bone mechanosensory cells that translate mechanical signals into biochemical, bone metabolism-regulating stimuli necessary for the adaptive process. Prostaglandins are an important part of this mechanobiochemical signaling. We investigated the signal transduction pathways in osteocytes through which mechanical stress generates an acute release of prostaglandin E 2 (PGE 2 ). Isolated chicken osteocytes were subjected to 10 min of pulsating fluid flow (PFF; 0.7 ± 0.03 Pa at 5 Hz), and PGE 2 release was measured. Blockers of Ca 2+ entry into the cell or Ca 2+ release from internal stores markedly inhibited the PFF-induced PGE 2 release, as did disruption of the actin cytoskeleton by cytochalasin B. Specific inhibitors of Ca 2+ -activated phospholipase C, protein kinase C, and phospholipase A 2 also decreased PFF-induced PGE 2 release. These results are consistent with the hypothesis that PFF raises intracellular Ca 2+ by an enhanced entry through mechanosensitive ion channels in combination with Ca 2+ - and inositol trisphosphate (the product of phospholipase C)-induced Ca 2+ release from intracellular stores. Ca 2+ and protein kinase C then stimulate phospholipase A 2 activity, arachidonic acid production, and ultimately PGE 2 release. osteocytes; mechanotransduction; prostaglandin E 2