Fluid shear stress increases interleukin-11 expression in human osteoblast-like cells: Its role in osteoclast induction

It is unclear how mechanical stress influences bone cells. Mechanical stres s causes fluid shear stress (FSS) in the bone. Osteoblast lineage cells are thought to sense FSS and regulate bone remodeling. We therefore investigat ed the effects of FSS on human osteoblast-like osteosarcoma cells: SaOS-2 c ells in vitro. The conditioned medium of the SaOS-2 cells after 24 h of FSS (24 h-FSS CM) showed such osteoclastic phenotype inductions as significant ly increasing the number of tartrate-resistant acid phosphatase (TRAP) posi tive multinuclear cells in rat bone marrow cells and TRAP-positive cells in human preosteoclastic cells: FLG 29.1 cells. An enzyme-linked immunosorben t assay showed interleukin-11 (IL-11) protein to increase 7-fold in the 24 h-FSS CM. A Northern analysis showed that IL-11 mRNA increased 4-fold in th e SaOS-2 cells after 6 h-FSS; however, no IL-6 mRNA expression was detected . Furthermore, the anti-human IL-11 antibody significantly neutralized the osteoclastic phenotype induction of the 24 h-FSS CM, The IL-11 mRNA up-regu lation in SaOS-2 cells by the 6 h-FSS was not inhibited by the anti-human t ransforming growth factor-pi antibody, but it was significantly inhibited b y indomethacin, An enzymeimmunoassay showed prostaglandin E-2 to increase 7 -fold in the 1 h-FSS CM, These findings thus suggest that FSS induces osteo blasts to produce IL-11 (mediated by prostaglandins) and thus stimulates bo ne remodeling.