Functional cross-talk of integrin b3 and AP-1 in differentiating osteoclasts and dendritic cells.

VAŇHARA, Petr, Kateřina SKÁLOVÁ, Eva ONDROUŠKOVÁ and Jan ŠMARDA. Functional cross-talk of integrin b3 and AP-1 in differentiating osteoclasts and dendritic cells. In Book of Abstracts. Warsaw: International Life Sciences Students's Conference, 2008, 2 pp. ISBN 978-83-927731-0-8.

Basic information

• Original name: Functional cross-talk of integrin b3 and AP-1 in differentiating osteoclasts and dendritic cells.
• Name in Czech: Funkční interakce integrinu beta 3 a AP-1 v diferencujících osteoklastech a dendritických buňkách
• Authors: VAŇHARA, Petr (203 Czech Republic), Kateřina SKÁLOVÁ (203 Czech Republic), Eva ONDROUŠKOVÁ (203 Czech Republic) and Jan ŠMARDA (203 Czech Republic, guarantor).
• Edition: Warsaw, Book of Abstracts, 2 pp. 2008.
• Publisher: International Life Sciences Students's Conference

Other information

• Original language: English
• Type of outcome: Proceedings paper
• Field of Study: Genetics and molecular biology
• Country of publisher: Poland
• Confidentiality degree: is not subject to a state or trade secret
• RIV identification code: RIV/00216224:14110/08:00024909
• Organization unit: Faculty of Medicine
• ISBN: 978-83-927731-0-8
• Keywords in English: osteoclasts; dendritic cells; integrin beta 3; AP-1
• Tags: AP-1, dendritic cells, integrin beta 3, osteoclasts
• Tags: International impact, Reviewed

Abstract

Osteoclasts (OCL) and dendritic cells (DC) are highly specialized cells that originate from a common hematopoetic progenitor. The osteoclasts are involved in bone resorption; dendritic cells represent a key compound of immune system as antigen presenting cells. Despite distinct functions, similar signaling molecules are involved in control of differentiation of OCL and DC. These regulators include integrin b3, the ECM receptor, and transcription factors c-Jun and c-Fos (AP-1). To investigate the signaling crosstalk between Itgb3 and AP-1 in OCL and DC, we employed murine model of RAW264.7 macrophages. These cells differentiate to OCL or DC upon treatment with RANKL (Receptor activator of NFkB ligand)MCSF or LPS (Lipopolysacharide). Expression of itgb3, c-jun and c-fos as well as differentiation markers were determined at mRNA level by qRT-PCR or western blotting. Expression of itgb3 was induced by both RANKL MCSF and LPS; however, expression of c-fos and c-jun was regulated differently in DC and OCL. Peptides containing Arg-Gly-Asp (RGD) sequence activate Itgb3 pathway specifically and induce expression of c-jun, c-fos and itgb3 in OCL but not in DC upon treatment with LPS. Similarly, inhibition of AP-1 by Jun N terminal kinase inhibitor (JNKi) increases expression of c-fos and itgb3, however it leaves expression of c-jun unaffected upon treatment with MCSF-RANKL or LPS. Moreover, JNKi, but not RGD, completely inhibits the M-CSF/RANKL-induced differentiation of RAW 264.7 cells to OCL and DC. We presume that there is mutual positive regulation between Itgb3- and c-Jun and c-Fos expression in OCL and DC.

Abstract (in Czech)

Osteoclasts (OCL) and dendritic cells (DC) are highly specialized cells that originate from a common hematopoetic progenitor. The osteoclasts are involved in bone resorption; dendritic cells represent a key compound of immune system as antigen presenting cells. Despite distinct functions, similar signaling molecules are involved in control of differentiation of OCL and DC. These regulators include integrin b3, the ECM receptor, and transcription factors c-Jun and c-Fos (AP-1). To investigate the signaling crosstalk between Itgb3 and AP-1 in OCL and DC, we employed murine model of RAW264.7 macrophages. These cells differentiate to OCL or DC upon treatment with RANKL (Receptor activator of NFkB ligand)MCSF or LPS (Lipopolysacharide). Expression of itgb3, c-jun and c-fos as well as differentiation markers were determined at mRNA level by qRT-PCR or western blotting. Expression of itgb3 was induced by both RANKL MCSF and LPS; however, expression of c-fos and c-jun was regulated differently in DC and OCL. Peptides containing Arg-Gly-Asp (RGD) sequence activate Itgb3 pathway specifically and induce expression of c-jun, c-fos and itgb3 in OCL but not in DC upon treatment with LPS. Similarly, inhibition of AP-1 by Jun N terminal kinase inhibitor (JNKi) increases expression of c-fos and itgb3, however it leaves expression of c-jun unaffected upon treatment with MCSF-RANKL or LPS. Moreover, JNKi, but not RGD, completely inhibits the M-CSF/RANKL-induced differentiation of RAW 264.7 cells to OCL and DC. We presume that there is mutual positive regulation between Itgb3- and c-Jun and c-Fos expression in OCL and DC.

Links

• GA301/06/0036, research and development project: Name: Úloha vybraných transkripčních faktorů v osteoklastové diferenciační dráze

Investor: Czech Science Foundation, A role of certain transcription factors in the osteoclastic differentiation pathway

• GD204/08/H054, research and development project: Name: Molekulární mechanismy proliferace a diferenciace buněk

Investor: Czech Science Foundation, Molecular mechanisms of the cell proliferation and differentiation

• MSM0021622415, plan (intention): Name: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations