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

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 κB 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. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 815-827, 2019.