Surface roughness mediates its effects on osteoblasts via protein kinase A and phospholipase A2

Earlier studies have shown that implant surface roughness influences osteoblast proliferation, differentiation, matrix synthesis and local factor production. Moreover, the responsiveness of osteoblasts to systemic hormones, such as 1,25-(OH)(2)D-3, at the implant surface is also influenced by surface roughness and this effect is mediated by changes in prostaglandins. At present, it is not known which signaling pathways are involved in mediating cell response to surface roughness and how 1,25-(OH)(2)D-3 treatment alters the activation of these pathways. This paper reviews a series of studies that have addressed this question. MG63 osteoblast-like cells were cultured on commercially pure titanium (cpTi) surfaces of two different roughnesses (R-a 0.54 and 4.92 mu m) in the presence of control media or media containing 1,25-(OH)(2)D-3 or 1,25-(OH)(2)D-3 plus H8 (a protein kinase A inhibitor) or quinacrine (a phospholipase A(2) inhibitor). At harvest, the effect of these treatments on cell number and alkaline phosphatase specific activity was measured. Compared to cultures grown on the smooth surface, cell number was reduced on the rough surface. 1,25-(OH)(2)D-3 inhibited cell number on both surfaces and inhibition of protein kinase A in the presence of 1,25-(OH)(2)D-3 restored cell number to that seen in the control cultures. Inhibition of phospholipase A(2) in the presence of 1,25-(OH)(2)D-3 caused a further reduction in cell number on the smooth surface, and partially reversed the inhibitory effects of 1,25-(OH)(2)D-3 on the rough surface. Alkaline phosphatase specific activity was increased in cultures grown on the rough surface compared with those grown on the smooth surface; 1,25-(OH)(2)D-3 treatment increased enzyme specific activity on both surfaces. Cultures treated with H8 and 1,25-(OH)(2)D-3 displayed enzyme specific activity that approximated that seen in control cultures. Inhibition of phospholipase A(2) also inhibited the 1,25-(OH)(2)D-3-dependent effect on the smooth surface, but on the rough surface there was an inhibition of the 1,25-(OH)(2)D-3 effect as well as a partial inhibition of the surface roughness-dependent effect. The results indicate that surface roughness and 1,25-(OH)(2)D-3 mediate their effects through phospholipase A(2), which catalyzes one of the rate-limiting steps in prostaglandin E-2 production. Further downstream, prostaglandin E-2 activates protein kinase A. (C) 1999 Elsevier Science Ltd. All rights reserved.