Arachidonic Acid and Prostaglandin E2 Influence Human Osteoblast (MG63) Response to Titanium Surface Roughness

Abstract

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.

Role of Prostaglandin E2 in the Modulation of Wnt Canonical Signaling in Cells on Microstructured Titanium Surfaces

“…Our findings are also at least partially supported by Dean et al, who reported that indomethacin increased ALP expression on micro rough discs in MG63 cells (31). Factors like PGE 2 or indomethacin dose and timing of application in culture have also been proven to be relevant in determining their overall effect, thus indicating that the action of PGE 2 is indeed complex and must be finely tuned (31,35). Moreover, the discovery of isoforms of PGE 2 receptors with distinct expression and effects must be taken into account when interpreting the results reported in the literature (39,40).…”

Response of human bone marrow stromal cells, MG‐63, and SaOS‐2 to titanium‐based dental implant surfaces with different topography and surface energy

“…In their study, Dean et al. () demonstrated that treatment of MG‐63 with 1–100 nM PGE 2 resulted in an increase of TNAP activity when cells were cultured on polished titanium surface and in a decrease of TNAP activity when cells were cultured on rough titanium surface. Considering MG‐63 as a kind of native drug delivery system, the amount of endogenously formed of PGE 2 (~0.85 nM) could be sufficient to cause the decrease of TNAP on both SBA surfaces.…”

Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling

“…34 demonstrated that PGE 2 could significantly inhibit osteocalcin production by human osteoblasts at concentrations as low as 1 nM 34 . Equivalent concentrations of PGE 2 were also shown to significantly impair ALP activity in human MG63 osteoblast-like cells 35 . More recently, PGE 2 was shown to effectively suppress hBMSC-mediated matrix mineralization 18 .…”