Factors Influencing Effects of Specific COX-2 Inhibitor NSAIDs on Growth and Differentiation of Mouse Osteoblasts on Titanium Surfaces

Purpose: To investigate the influence of exposure time and stages of cell growth on the effects of specific COX-2 inhibitor NSAIDs on growth and differentiation of osteoblasts on smooth titanium surfaces. Materials and Methods: The study was categorized into 5 groups: group A, 0.1 µM indomethacin; group B, 1.5 µM celecoxib; group C, 3.0 µM celecoxib; group D, 9.0 µM celecoxib; and group E, serum-free culture medium without drug treatment. A mouse calvarial cell line, MC3T3-E1, was seeded on acid-prickled surface titanium disks. The investigations were performed in 3 experimental phases based on stages of cell growth: static (24 hours after seeding), log (culture day 5), and plateau (culture day 12). In each experimental phase, cells on titanium disks were incubated in a medium treated with drugs according to the groups of study for 1, 3, and 5 days. Results: Indomethacin and celecoxib in groups A to D inhibited growth of cells on treatment days 3 and 5 in static phase and on treatment day 3 in log phase. Additionally, an inhibitory effect of indomethacin was greater than celecoxib. Effects on alkaline phosphatase (ALP) activity and osteocalcin were not clearly demonstrated. A significant decrease of PGE2 production was found in groups A to D in static and plateau but not log phases. Conclusion: A specific COX-2 inhibitor NSAID, celecoxib, inhibited growth of osteoblasts on titanium surfaces and the effects were influenced by exposure time and stages of cell growth. Using a specific COX-2 inhibitor might cause deterioration of osteointegration of dental implants by interfering with osteoblastic cell growth in the proliferative stage. Keywords: growth and differentiation, osteoblasts, specific COX-2 inhibitor NSAIDs, titanium surface