Inhibition of signaling cascades in osteoblast differentiation and fibrosis

Leiden Repository

Inhibition of signaling cascades in osteoblast differentiation and fibrosis

Type: Doctoral thesis
Title: Inhibition of signaling cascades in osteoblast differentiation and fibrosis
Author: Krause, Carola
Publisher: Department Molecular Cellbiology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2011-10-05
Keywords: BMP
Dupuytren's disease
Fibrosis
Noggin
Osteoblast Differentiation
Osteoporosis
Sclerostin
Signaling Cascades
TGF-beta
Signaling Drifts
Abstract: The basis of the presented investigations in this thesis is the modulation of signal inducers and their respective activated signaling cascades through intrinsic antagonistic feedback- and/or feed forward-loops. In particular, signal inducers of the transforming growth factor-β superfamily were investigated on their impact on tissue development and maintenance. Thereby, the main focus lies on a group of proteins that are known as bone morphogenetic proteins (BMPs). Due to their wide impact, Dr. H. Reddi recently proposed a more suitable name to this cytokines: body morphogenetic proteins. The distinct terminology is also reflected in this book. Not only does this book discuss the impact of BMP signal modulation on osteoblast differentiation, it also focuses on BMPs as potential inducers of signaling drifts in fibrotic traits. Interestingly, BMPs can relay signals with different outcomes. They can be signal triggers themselves as investigated in the case of osteoblast differentiation, but they can also arrest signaling cascades, as shown for TGF-β induced fibrosis. Up to date, more than fifteen different BMPs are known. One aim of this book is to biochemically characterize different BMPs on their potential to relay signals and how this signals can be governed to yield a specific medical benefit. It is well known that BMPs are tightly regulated on diverse interfaces throughout the cell. Thereby, the presented investigations focus on innate extracellular signaling modulators, as well as on synthetic small molecule inhibitors that have the potential to facilitate the development of new treatment strategies of certain human diseases.
Description: Promotor: Peter ten Dijke
With summary in Dutch
Faculty: LUMC
Citation: Krause, C., 2011, Doctoral thesis, Leiden University
ISBN: 9789064645020
Handle: http://hdl.handle.net/1887/17892
 

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