The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors

Autor: Melanie Krug, Franz Jakob, Peggy Benisch, Sönke P. Frey, S. Zeck, Michael Amling, Tatjana Schilling, Regina Ebert, Ludger Klein-Hitpass, Thorsten Schinke, N. Raaijmakers, Martina Regensburger, Lothar Seefried
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Aging
Candidate gene
Anatomy and Physiology
Osteopenia and Osteoporosis
Medizin
lcsh:Medicine
Transcriptome
Molecular cell biology
Bone Density
Osteogenesis
Risk Factors
Cluster Analysis
Signaling in Cellular Processes
lcsh:Science
Cellular Senescence
WNT Signaling Cascade
Oligonucleotide Array Sequence Analysis
Aged
80 and over
Multidisciplinary
ddc:617
Stem Cells
LRP5
Middle Aged
Beta-Catenin Signaling
Signaling Cascades
Medicine
Female
Cellular Types
Stem cell
Cell aging
Research Article
Signal Transduction
DNA transcription
Bone Marrow Cells
Biology
Humans
Genetic Predisposition to Disease
Epigenetics
Bone regeneration
Aged
Smad Signaling
Gene Expression Profiling
lcsh:R
Mesenchymal stem cell
Mesenchymal Stem Cells
equipment and supplies
Gene Expression Regulation
Immunology
Cancer research
Osteoporosis
Women's Health
lcsh:Q
Gene expression
Physiological Processes
Osteoporotic Fractures
Developmental Biology
Zdroj: PLoS ONE, Vol 7, Iss 9, p e45142 (2012)
PLoS ONE
Popis: 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 ~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. © 2012 Benisch et al.
Databáze: OpenAIRE
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