Prior studies have shown that implant surface roughness affects osteoblast proliferation, differentiation, matrix synthesis, and local factor production. Further, cell response is modulated by systemic factors, such as
1,25(OH)2D3 and
estrogen as well as mechanical forces. Based on the fact that peri-implant bone healing occurs in a site containing elevated amounts of
prostaglandin E2 (
PGE2), the hypothesis of the current study is that
PGE2 and
arachidonic acid (AA), the substrate used by
cyclooxygenase to form
PGE2, influence osteoblast response to implant surface roughness. To test this hypothesis, 4 different types of commercially pure
titanium (cpTi) disks with surfaces of varying roughness (smooth Ti, R(a) 0.30 microm; smooth and
acid etched Ti [SAE Ti], R(a) 0.40 microm; rough Ti, R(a) 4.3 microm; rough and
acid etched Ti [RAE Ti], R(a) 4.15 (microm) were prepared. MG63 osteoblasts were seeded onto the surfaces, cultured to confluence, and then treated for the last 24 hours of culture with AA (0, 0.1, 1, and 10 nM),
PGE2 (0, 1, 10, 25, and 100 nM), or the general
cyclooxygenase inhibitor indomethacin (0 or 100 nM). At harvest, the effect of treatment on cell proliferation was assessed by measuring cell number and [3H]-
thymidine incorporation, and the effect on cell differentiation was determined by measuring
alkaline phosphatase (ALP) specific activity. The effect of AA and
PGE2 on cell number was somewhat variable but showed a general decrease on
plastic and smooth surfaces and an increase on rough surfaces. In contrast, [3H]-
thymidine incorporation was uniformly decreased with treatment on all surfaces. ALP demonstrated the most prominent effect of treatment. On smooth surfaces, AA and
PGE2 dose-dependently increased ALP, while on rough surfaces, treatment dose-dependently decreased
enzyme specific activity.
Indomethacin treatment had either no effect or a slightly inhibitory effect on [3H]-
thymidine incorporation on all surfaces. In contrast,
indomethacin inhibited ALP on smooth surfaces and stimulated ALP on rough. Taken together, the results indicate that both AA and
PGE2 influence osteoblast response by promoting osteoblast differentiation on smooth surfaces, while inhibiting it on rough surfaces. Because implants with rough surfaces are acknowledged to be superior to those with smooth surfaces, these results suggest that use of nonsterioidal anti-inflammatory drugs to block
PGE2 production and reduce
inflammation may be beneficial in the postoperative period after implant placement. They also indicate that manipulation of the AA metabolic pathway may offer a new therapeutic approach for modulating bone healing after implant placement. Because peri-implant healing takes place in a complex cellular environment quite different from the one used in the present study, additional work will be necessary to substantiate these possibilities.