Characterization of Heat Shock Proteins production and activity in osteblasts and their role in mechanical stress

• Grant number: 11/18835-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Dentistry - Orthodontics
• Principal Investigator: Adalberto Luiz Rosa
• Grantee: Thiago Pompermaier Garlet
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The bone tissue supports and protects the most soft and fragile tissues in the human body, thus requiring resistance without excessive weigh that would overburden the muscles. In order to achieve this goal efficiently, complex mechanisms of bone remodeling and repair are orchestrated by hormones and immune cytokines; such interaction has been ultimately nominated Osteoimmunology. Recently the study of sterile inflammatory processes has been increasing, especially when factors known as DAMPs are involved, and so has the interest in the role played by these factors in bone biology. DAMPs are damage-associated molecular patterns, released by cells under different kinds of stress and also necrotic tissues, that are capable of activating the immune system in a similar way to bacterial products. One of the most well known DAMPs, namely HMGB1, has already been studied in bone cells and had its effects characterized, suggesting a role for this mediator class in bone remodeling. Thus, we propose the study of another mediator also considered a DAMP and possibly involved in this process: the heat shock proteins. Heat shock proteins are mediators produced by cells after stressful stimuli, such as heat shock and pH variations, among others. High levels of these proteins have been found in orthodontic patients' gingival fluid, suggesting that mechanical stress could also be a trigger to heat shock protein production. Heat shock proteins are important in protein folding and help cells to survive through stressful conditions, and have also been described as DAMPs when released to extracellular medium, sharing mechanisms of action with HMGB1. That considered, the objectives of this study are to characterize the production and activity of heat shock proteins in osteoblasts in vivo; and to assess the expression of these proteins in orthodontic tooth movement, both human and experimental. We believe that a deeper understanding of heat shock protein production and function in bone cells, paired with the knowledge of the roles played by these proteins in orthodontic tooth movement might strengthen the basic theoretical foundations needed to shed light on the mechanisms of bone remodeling driven by mechanical forces.