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Titanium (Ti) possesses excellent properties for use in dental implants but has low osteogenic surface properties that result in limiting rapid osseointegration. The physiological interaction between the surface of the implant material and bone cells, especially osteoclasts, is a crucial factor in determining successful osseointegration. However, the details of such an interaction remain elusive. Here, we demonstrated that nanotopography on the Ti surface is a crucial factor for modulating intracellular signal transduction in bone marrow-derived macrophages (BMMs). To define this, intracellular Ca2+ and ROS were simultaneously measured in BMMs that were seeded on polished Ti and TiO2 nanotubes. We found that UV photocatalysis of TiO2 immediately elicits intracellular calcium concentration ([Ca2+]i) increase and intracellular reactive oxygen species concentration ([ROS]i) reduction in cells on TiO2 nanotubes. UV photocatalysis-mediated [Ca2+]i increase is dependent on extracellular and intracellular ROS generation. Furthermore, extracellular Ca2+ influx through voltage-gated calcium channels (VGCCs) is critical for the UV photocatalysis-mediated [Ca2+]i increase, while phospholipase C (PLC) activation is not required. Considering the physiological roles of Ca2+ signaling in BMMs and osteoclastogenesis, nanotopography on the Ti surface should be considered an important factor that can influence successful dental implantation.

UV Photocatalysis of Bone Marrow-Derived Macrophages on TiO2 Nanotubes Mediates Intracellular Ca2+ Influx via Voltage-Gated Ca2+ Channels