Tensile Force Promotes Osteoclastogenesis through RANKL Pathway

Objective: Little is known about the effects of tensile forces on osteoclastogenesis by macrophage in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study we consider the effects of tensile force on osteoclastogenesis in human monocytes. Method: The cells were isolation from blood, than treated with RANKL and tensile force to promote osteoclastgenesis. The cells’ viability and osteoclastgenic differentiation markers are determined by using PrestoBlue® assay and western blot, respectively. A one-way variance statistical analysis was used to evaluate the significance of the differences between the groups in each experiment. Result: There was no significant difference of cell viability between different tensile forces. It was also found that ≤ -50 kPa induces RANKL-enhanced TRAP activity in a dose-dependent manner. The increased tensile force raises the expression and secretion of cathepsin K elevated by RANKL, and is concurrent with the increase of TRAF6 induction and NF-ƘB activation. Conclusion: The tensile force is able to modify every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, affecting the fusion of pre-osteoclasts, and function of osteoclasts. However, tensile force increased TRAF6 expression. Although these are in vitro findings and were gained under a condition of tensile force, the current results help us to better understand the cellular roles of human macrophage cell populations in osteoclastogenesis as well as in alveolar bone remodeling when there is tensile stress.