RXR IN MYELOID CELLS

Contribution of RXRs to myeloid cell biology: from hematopoietic stem cells to osteoclastogenesis

Coordinatore	FUNDACION CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III    more  Organization address address: C/ MELCHOR FERNANDEZ ALMAGRO 3 city: MADRID postcode: 28029 contact info Titolo: Dr. Nome: Mercedes Cognome: Ricote Email: send email Telefono: +34 91 453 1200 Fax: + 34 91 453 1245
Nazionalità Coordinatore	Spain [ES]
Totale costo	45˙000 €
EC contributo	45˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-RG
Funding Scheme	MC-ERG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-09-01   -   2013-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACION CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III  Organization address address: C/ MELCHOR FERNANDEZ ALMAGRO 3 city: MADRID postcode: 28029 contact info Titolo: Dr. Nome: Mercedes Cognome: Ricote Email: send email Telefono: +34 91 453 1200 Fax: + 34 91 453 1245	ES (MADRID)	coordinator	45˙000.00

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 Obiettivo del progetto (Objective)

'Hematopoietic stem cells (HSCs) yield blood precursors devoted to unilineage differentiation and production of mature blood cells, including red blood cells, megakaryocytes, lymphocytes and myeloid cells. Precursors of the myeloid lineage differentiate into monocytes and granulocytes but at given stages of their maturity they can be also sources of multinucleated osteoclasts. Consequently, any altered myelopoiesis can be directly linked to deficiencies in osteclastogenesis and impaired bone homeostasis. Retinoic X receptors (RXRa, RXRb and RXRg) are members of the nuclear receptor family. They appear to contribute to hematopoiesis and osteoclastogenesis via their roles as heterodimeric partners of several nuclear receptors. Functionally the most important isotype is RXRa during morphogenesis. Since RXRs can function either as homodimers or heterodimers, it is unclear whether the effects of RXRs on hematopoiesis and osteoclastogenesis are coupled to RXR homodimers, heterodimers, or involve the regulation of parallel pathways. Additionally, in mouse models of RXRa deletion, a partial redundancy in RXRa, b and g functions can be also observed. In this context, the goal of the presented project is to characterize the role of RXRs in HSC differentiation and osteoclastogenesis. In this project we will work with a knockout mouse model in which both RXRa and RXRb are selectively ablated in the hematopoietic system. Using this model we will be able to characterize the in vivo effects of the conditional inhibition of RXRa and b in the murine hematopoietic system and we can clarify the contribution of each isoforms to myeloid cell differentiation and osteoclastogenesis. The results are anticipated to open new perspectives for developing stem cell based therapies for the treatment of bone-related diseases such as osteoporosis or rheumatoid arthritis, nowadays affecting hundreds of millions of people worldwide.'