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Assessment of pathway RANKL osteoclast activation in osteoblasts derived from human adipose tissue

Grant number: 09/51727-2
Support type:Regular Research Grants
Duration: August 01, 2009 - December 31, 2012
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Celia Regina Nogueira
Grantee:Celia Regina Nogueira
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The regulation of bone remodeling occurs through local and systemic factors that act on the replication of undifferentiated cells, recruitment and function of bone cells. Among local factors, the system osteoprotegerin (OPG) / receptor activator of NF-kB (RANK) / RANK ligand (RANKL), indicates that the process of resorption and formation are coupled. The interaction between RANK and RANKL pathway is best known in osteoclast differentiation and activation. The RANK promotes osteoclast maturation by increasing the expression of specific genes, including the transcription factor c-Fos. Estrogen and thyroid hormones directly affect bone metabolism. The T3 increases the expression of RANKL in pre-osteoblastic cells, activating the osteoclastogenesis. Adequate levels of estrogen in the body to ensure removal of cytokines that induce the proliferation and differentiation of osteoclasts. However, there are indications that the process of osteoclast activation can be independent of the RANK / RANKL, particularly when induced by thyroid hormones. This study will allow to obtain important information on the influence of thyroid hormone, associated with estrogen, the pathway of osteoclast activation. The use of human osteoblasts, originating from mesenchymal stem cells from adipose tissue, is the type of study used, with the objective to obtain results closer to normality, increasing its clinical application. (AU)