Mechanical loading induced osteocyte apoptosis and connexin 43 expression in three-dimensional cell culture and dental implant model.

Osteocytes are thought to act as stress sensors, and are known to display a gap junction-mediated stress-transfer mechanism. To demonstrate the stress-related function of osteocytes, cells of an osteocyte-like cell line derived from murine long bone osteocyte Y4 (MLO-Y4) were cultivated in a three-dimensional culture and subjected to cyclic loading from a titanium plate. This application of physiological loading using a titanium plate significantly increased connexin 43 (Cx43) expression, the number of dead and apoptotic cells, and receptor activator of nuclear factor kappa B ligand expression. Furthermore, the conditioned medium from the loaded osteocytes induced alkaline phosphatase activity in bone marrow cell culture. In addition, we immunohistologically determined whether bone metabolism increased as a result of the occlusal force in the bone surrounding the titanium implants in a rat model. Increased Cx43 expression and apoptotic osteocytes were observed in the loading group as well as a significantly increased number of tartrate-resistant acid phosphatase-positive cells. These findings indicate that stress from the implant adversely affected the osteocytes, which may promote osteoclastic and osteoblastic cell formation around the implants. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 815-827, 2019.