The role of inflammation and use of glucocorticoids in a mouse model of osteoporosis associated with collagen induced arthritis

• Grant number: 12/10570-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2012
• End date: February 28, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Charlles Heldan de Moura Castro
• Grantee: Charlles Heldan de Moura Castro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Daniela Vargas Horvath ; Marina Eloi

Abstract

Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by bone complications, including osteoporosis. In RA, periarticular bone loss, bone erosions and systemic osteoporosis are observed, with an increased risk of fractures. The contribution of the inflammatory process and the use of glucocorticoids as determinants of osteoporosis in RA are not well determined. In this study, we will investigate the effects of arthritis and glucocorticoid use on bone loss associated with collagen type II induced arthritis (CIA). DBA/1 male mice (10 animals per group, age 4 months) will be treated for 8 weeks with prednisolone (5 mg / kg of slow release pellets subcutaneously). CIA will be produced by standard technique 2 weeks after initiation of the protocol. The effect of arthritis and glucocorticoid use in the model of osteoporosis will be tested in four experimental groups: A: control, B: control + prednisolone; C: CIA, D: CIA + prednisolone. Bone mineral density (BMD) will be measured by DXA at the initial time and after 4 and 8 weeks of treatment, whereas the bone remodeling in vivo will be measured by serum PINP and CTX at the end of the study. Joint damage and erosion will be investigated by histopathological score. Static and dynamic bone histomorphometry will be performed in all groups at the end of the protocol to determine the effects of arthritis and glucocorticoid use on bone formation and resorption. In vitro bone mineralization, alkaline phosphatase activity and the expression of osteoblast marker genes (measured by real time PCR) will be investigated in cultured stromal cells from bone marrow extracted from different study groups at the end of the experiment. The study hopes to determine the relative contribution of inflammation and glucocorticoid use on bone loss associated with CIA. (AU)