Role of mitofusin 2 and mitochondrial dynamics on osteoclasts bone resportion in an Osteoarthritis experimental model

Abstract

Osteoclasts are single cells with the bone resorption function. This function demands a high energetic load, so it is believed that mitochondria, organelles abundant in osteoclasts, participate in the metabolic reconfiguration that occurs during the processes of differentiation and cellular activation. It is known that mitochondria change in number, size and conformation in a process called mitochondrial dynamics, which is divided into mitochondrial fusion and fission. Mitochondrial dynamics are regulated by a network of molecules, one of which is mitofusin 2 (Mfn 2). Mfn2 plays an important role in metabolic regulation and is also an important factor in cell survival. Considering the role of Mn2 in the mitochondrial fusion process and the role of mitochondrial dynamics in the context of osteolytic disease is still unknown, the present project intends to evaluate the importance of mitochondrial behavior and dynamics in osteoclasts on the process of osteoclastogenic differentiation in vitro as well as on bone resorption in an experimental model of bone loss. Initially, we intend to characterize the morphofunctional changes of the mitochondria during osteoclast differentiation in vitro. Next, we will evaluate the effect of Mfn2 selective deletion on osteoclast (CtpskCre Mfn2flox / flox mice, and their respective controls), on mitochondrial morphofunctional characteristics and energetic metabolism during osteoclast differentiation and activation in vitro. We will also evaluate the involvement of Mfn2 during the osteolytic disease process in the knee joint of animals (CtpskCre Mfn2flox/flox mice, and their respective controls) submitted to the experimental model of Osteoarthritis. (AU)