A role of certain transcription factors in the osteoclastic differentiation pathway

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Project Identification
Project Period
1/2006 - 12/2008
Investor / Pogramme / Project type
Czech Science Foundation
MU Faculty or unit
Faculty of Science
Myb, Fos, Pu-1, MITF, osteoclast, differentiation, monocyte, macrophage, hematopoiesis

Osteoporosis is one of the leading causes of morbidity in the elderly and is characterized by a progressive loss of total bone mass and bone density. Bone loss in osteoporosis is due to the persistent excess of osteoclastic bone resorption over osteoblastic bone formation. Osteoclasts are cells of hematopoietic origin and their formation is controlled by multiple transcription factors. The aim of this proposal is to define the role of PU.1, MITF, Myb, Fos and NFB transcription factors in regulation of monoblasts/macrophages towards osteoclasts. The project is based (1) on analyses of expression of these transcription factors during induced differentiation of the cells of monoblastic (BM2) and macrophage (RAW) cell lines, (2) on targeted induction or repression of expression of the genes coding for these transcription factors in BM2 and RAW cells and detailed analyses of the effects resulting from changed expression profiles on differentiation capabilities of these cells. The conlusions about the function of the transription factors in control of osteoclast differentiation made on established cell lines are going to be verified on primary FL cells, that can be induced to differentiate towards dendritic cells, macrophages, microglial cells and osteoclasts by various growth factors. The elucidation of molecular mechanisms governing bone-cell differentiation is of particular importance considering the incidence and severity of the diseases that affect skeletal development.


Total number of publications: 28

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