Role of glycolysis in osteoclasts function

• Grant number: 21/13934-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Rafaela Braun Araújo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

Osteoclasts are giant, multinucleated cells derived from the fusion of myeloid progenitors; their importance is due to the fact that they are the only cells in the human body responsible for the bone resorption function. To perform this function, osteoclasts undergo a series of structural and biochemical adaptations that demand a high energy load. Therefore, studies aimed at reducing osteoclast activity in osteolytic diseases such as osteoporosis and osteoarthritis have been seeking to understand and modulate osteoclast metabolism. When it comes to metabolism, glycolysis is the process by which, in the absence of oxygen, glucose is transformed into lactic acid (lactate) with the production of two molecules of ATP. However, in some cells there is energy production via glycolytic even in the presence of oxygen, this phenomenon is called aerobic glycolysis or the Warburg effect. There is evidence that during osteoclast differentiation, energy production via oxidative phosphorylation is preferred by osteoclasts, but during osteoclast function, it is possible to observe a high expression of molecules associated with the glycolytic pathway such as PKM2 and GAPDH near the ruffle border, where bone resorption occurs. Therefore, the aim of this project is to evaluate the role of glycolysis during osteoclast resorption function. For this, the expression of molecules of the aerobic glycolysis pathway (PKM2) will be evaluated during osteoclast differentiation. The differentiation and function of osteoclasts in vitro in osteoclasts with macrophages conditional PKM2 knockout (LysMcre/0PKM2f/f) will be evaluated, as well as the number and function of osteoclasts in vivo in osteoclast conditional PKM2 knockout mice (Ctpskcre/0PKM2f/f). The metabolism of these osteoclasts will be evaluated by oxygen consumption and extracellular acidification.(AU)