TY - THES A1 - Raaijmakers, Nadja T1 - Osteoporoseprophylaxe mit pflanzlichen Wirkstoffen T1 - Osteoporosis prevention with plant ingredients N2 - Osteoporose ist einer der häufigsten Knochenerkrankungen im fortschreitenden Alter und zählt, aufgrund der damit verbundenen hohen direkten und indirekten Behandlungskosten, zu einer der zehn wichtigsten volkswirtschaftlichen Krankheiten. Die Behandlung der Osteoporose ist langjährig und umfasst eine medikamentöse Therapie auf der Basis einer „knochengesunden“ Lebensweise hinsichtlich Ernährung und Bewegung. Im Rahmen von Untersuchungen zur Linderung von postmenopausalen Beschwerden, zeigte ein Extrakt der Pflanze Cimicifuga racemosa Potential zu osteoprotektiver Wirksamkeit und rückte somit in den Fokus für eine mögliche Anwendung in der Therapie und Prophylaxe von Osteoporose. Das Ziel der vorliegenden Arbeit war es daher, in enger Zusammenarbeit mit der Bionorica SE, welche für die Aufreinigung und Fraktionierung des Pflanzenextraktes zuständig war, und mit der Arbeitsgruppe um Prof. Wuttke, welche parallele Rattenstudien durchführte, Methoden anzuwenden, mit denen osteoprotektive Wirksamkeiten nachgewiesen und auf einzelne Fraktionen des Extraktes limitiert werden können. ... N2 - Osteoporosis is one of the most common bone diseases in advancing age and is, due to the associated high direct and indirect costs of treatment, one of the ten most important economic diseases. The treatment of osteoporosis lasts for many years and covers a drug therapy based on a "bone-healthy" lifestyle regarding diet and exercise. As part of investigations for the relief of postmenopausal symptoms Cimicifuga racemosa showed potential to osteoprotective effectiveness and thus the focus places special emphasis to the potential application in the treatment and prevention of osteoporosis. The aim of the present study was therefore, in close cooperation with the Bionorica SE, which was responsible for the purification and fractionation of the plant extract and the research group of Professor Wuttke, which conduct parallel rat studies, to investigate methods which demonstrate osteoprotective efficacies and may be limited to individual fractions of the extract. ... KW - Osteoporose KW - Prävention KW - Traubensilberkerze KW - humane mesenchymale Stammzellen KW - Differenzierung KW - osteoprosis KW - prevention KW - black cohosh KW - human mesenchymal stem cells KW - differentiation KW - Arzneimittelforschung KW - Phytopharmakon Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-83341 ER - TY - JOUR A1 - Benisch, Peggy A1 - Schilling, Tatjana A1 - Klein-Hitpass, Ludger A1 - Frey, Sönke P. A1 - Seefried, Lothar A1 - Raaijmakers, Nadja A1 - Krug, Melanie A1 - Regensburger, Martina A1 - Zeck, Sabine A1 - Schinke, Thorsten A1 - Amling, Michael A1 - Ebert, Amling A1 - Jakob, Franz T1 - The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors JF - PLoS One N2 - Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79-94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of similar to 30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP. Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process. KW - alkaline-phosphatase KW - in vitro KW - bone-mineral density KW - age-related osteoporosis KW - WNT signaling pathway KW - replicative senescence KW - morphogenetic protein KW - parathyroid-hormone KW - growth factor KW - skeletal overexpression Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133379 VL - 7 IS - 9 ER -