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Grant number: 11/18609-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2011
Effective date (End): May 31, 2016
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:João Bosco Pesquero
Grantee:Fernanda Rossell Malinsky
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:08/06676-8 - Cellular and molecular biology of the kallikrein-kinin and renin-angiotensin systems, AP.TEM


Fibrodysplasia ossificans progressiva (FOP) is the most extensive heterotopic osteogenesis disorder, resulting in an ectopic post-natal bone and is one of the most rare diseases that affect humans. The diagnosis of FOP can be performed through clinical and radiographic examination and nowadays there is not a specific and effective treatment for FOP. A mutation in the gene encoding the activin receptor was identified as responsible for the disease phenotype. This mutation causes overactivation of the signaling pathway of bone morphogenetic protein-4 (BMP-4), which is the cause of heterotopic osteogenesis, and is found upregulated in this disease. Histological evaluations have shown that a muscle inflammation that occurs gradually turns into bone. FOP is a disease characterized by inflammation at the start with lymphocytic infiltrate, and could have a possible relationship with bradykinin, since this molecule is linked to inflammation. Our team has been working with knockout animals for the kinin receptors B1, B2 and B1B2 and their involvement in bone metabolism and bone formation process. This project aims to investigate the functions of kinin receptors B1 and B2 in osteogenesis as well as heterotopic osteogenesis induced by the exogenous admoinistration of BMP-4, mimicking the phenotype shown in FOP. The use of this animal model of FOP, generated by the injection of exogenous BMP-4 will allow us to clarify the role of the inflammation mediated by kinins in ectopic bone formation, found in this disease. Blockade of kinin receptors using drugs may become an interesting therapy and this project may provide support for future research which main objective is the development of a therapy for the modulation of the osteogenic processes in the bone tissue.

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