Light-induced Membrane Hyperpolarization Promotes Osteoblast Differentiation in MC3T3 Osteoblast-like Cells

Bone mass is regulated by bone remodeling, which involves bone formation by osteoblasts and bone resorption by osteoclasts. To prevent and treat bone loss, a basic understanding of the mechanism of bone formation is essential, including osteoblast differentiation, and its responses to mechanical stimuli that induce changes in membrane potential. During osteoblast differentiation, hyperpolarized membrane potential was observed. To understand osteoblast differentiation in response to membrane hyperpolarization, as well as the long-term effects of changes in membrane potential, we developed a light-controllable membrane potential system in MC3T3-E1 osteoblast-like cells by stably expressing the light-driven outward proton pump, archaerhodopsin-3. Archaerhodopsin-3 activation by yellow-green light hyperpolarizes the cell membrane Light-induced hyperpolarization accelerated osteoblast mineralization, as assessed by Alizarin Red staining, alkaline phosphatase activity, and expression levels of osteoblast differentiation markers. This promotion of osteoblast mineralization is related to voltage-gated Ca channels. Our study revealed a novel role of membrane potential in non-excitable osteoblast-like cells.