Osteocyte Involvement in Peri-implant Strain-related Bone Remodeling

Objectives: Osteocytes are believed to be mechanosensors and responsible for coordinating bone remodeling process. The occlusal force acting on dental implants directly and intricately transfer to the alveolar bone. We hypothesized that osteocytes neighboring implant should play an important role in detecting local mechanical environment and in initiating bone remodeling process. However, little is known about how osteocytes response to mechanical stress received from implant. The aim of this study was to investigate the effects of force-induced biochemical response of osteocytes in vitro.
Methods: We established two types of loading apparatuses, in which MLO-Y4 osteocyte cell line was three-dimensionally cultured, subjected to the application of cyclic mechanical stress in physiological strain for 24 hours. One could simultaneously apply five kinds of (from 0.095% to 1.22%) stretching force to the cells (n=4/gp). The other was an apparatus that the titanium plate which imitated dental implant screw shape could apply cyclic stress to the cell-embedded gel (n=4/gp). Cell viability assay and real-time RT-PCR analysis were examined. Additionally, the conditioned media from stimulated cultures were added to bone marrow cultures and ALP activity was measured. Moreover, inhibition of gap junction channels was performed using inhibitor (heptanol). Results were statistically analyzed (ANOVA, p<0.05 as significance).
Results: Cyclic physiological strain applied by both devices induced the cell death of MLO-Y4. Real-time RT-PCR analyses showed that the mechanical strain increased RANKL/OPG ratio and suppressed sclerostin expression in a magnitude-dependent manner. Connexin43 expression increased in the middle strain magnitude. The conditioned medium obtained from low magnitude cyclic stretch culture increased ALP activity of bone marrow culture. This increase was supressed by the inhibition of gap junction.
Conclusions: These results suggest that the gap junction signaling of osteocytes plays some roles in regulating peri-implant strain-related bone remodeling.