The P2X7 nucleotide receptor is an ATP-gated ion channel expressed widely in cells of hematopoietic origin. Our purpose was to explore the involvement of the P2X7 receptor in bone development and remodeling by characterizing the phenotype of mice genetically modified to disrupt the P2X7 receptor [knockout (KO)]. Femoral length did not differ between KO and wild-type (WT) littermates at 2 or 9 months of age, indicating that the P2X7 receptor does not regulate longitudinal bone growth. However, KO mice displayed significant reduction in total and cortical bone content and periosteal circumference in femurs, and reduced periosteal bone formation and increased trabecular bone resorption in tibias. Patch clamp recording confirmed expression of functional P2X7 receptors in osteoclasts from WT but not KO mice. Osteoclasts were present in vivo and formed in cultures of bone marrow from KO mice, indicating that this receptor is not essential for fusion of osteoclast precursors. Functional P2X7 receptors were also found in osteoblasts from WT but not KO mice, suggesting a direct role in bone formation. P2X7 receptor KO mice demonstrate a unique skeletal phenotype that involves deficient periosteal bone formation together with excessive trabecular bone resorption. Thus, the P2X7 receptor represents a novel therapeutic target for the management of skeletal disorders such as osteoporosis.

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Stanton numbers, skin friction coefficients, aerodynamic losses, and Reynolds analogy behavior are numerically predicted for a turbine vane using the FLUENT commercial code with a k-e RNG model to show the effects of Mach number, mainstream turbulence level, and surface roughness. Test vane geometry, configuration, and flow conditions match ones from a practical application. Comparisons with experimental data on wake aerodynamic losses are made. Numerical and experimental results show that the magnitudes of integrated aerodynamics losses increase dramatically as the exit Mach number increases from 0.35 to 0.71. Downstream wakes are also widened as the mainstream turbulence intensity level, exit Mach number, or level of surface roughness increases. Deviations of numerically predicted 2 St=C f magnitudes from 2 St=C f ffi 1 on the vane suction and pressure sides are also presented for a variety of flow conditions.