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

Hdl Handle:
http://hdl.handle.net/10675.2/828
Title:
The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors
Authors:
Benisch, Peggy; Schilling, Tatjana; Klein-Hitpass, Ludger; Frey, Sonke P.; Seefried, Lothar; Raaijmakers, Nadja; Krug, Melanie; Regensburger, Martina; Zeck, Sabine; Schinke, Thorsten; Amling, Michael; Ebert, Regina; Jakob, Franz ( 0000-0001-6560-8437 )
Abstract:
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 (79â 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 â ¼30 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.
Editors:
Shi, Xing-Ming
Citation:
PLoS One. 2012 Sep 24; 7(9):e45142
Issue Date:
24-Sep-2012
URI:
http://hdl.handle.net/10675.2/828
DOI:
10.1371/journal.pone.0045142
PubMed ID:
23028809
PubMed Central ID:
PMC3454401
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Pathology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorBenisch, Peggyen_US
dc.contributor.authorSchilling, Tatjanaen_US
dc.contributor.authorKlein-Hitpass, Ludgeren_US
dc.contributor.authorFrey, Sonke P.en_US
dc.contributor.authorSeefried, Lotharen_US
dc.contributor.authorRaaijmakers, Nadjaen_US
dc.contributor.authorKrug, Melanieen_US
dc.contributor.authorRegensburger, Martinaen_US
dc.contributor.authorZeck, Sabineen_US
dc.contributor.authorSchinke, Thorstenen_US
dc.contributor.authorAmling, Michaelen_US
dc.contributor.authorEbert, Reginaen_US
dc.contributor.authorJakob, Franzen_US
dc.contributor.editorShi, Xing-Ming-
dc.date.accessioned2012-10-26T20:35:12Z-
dc.date.available2012-10-26T20:35:12Z-
dc.date.issued2012-09-24en_US
dc.identifier.citationPLoS One. 2012 Sep 24; 7(9):e45142en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid23028809en_US
dc.identifier.doi10.1371/journal.pone.0045142en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/828-
dc.description.abstractPrimary 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 (79â 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 â ¼30 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.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectDevelopmental Biologyen_US
dc.subjectStem Cellsen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Typesen_US
dc.subjectStem Cellsen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.subjectBone Marrow Cellsen_US
dc.subjectGene Expressionen_US
dc.subjectDNA transcriptionen_US
dc.subjectSignal Transductionen_US
dc.subjectSignaling Cascadesen_US
dc.subjectWNT Signaling Cascadeen_US
dc.subjectSignaling in Cellular Processesen_US
dc.subjectBeta-Catenin Signalingen_US
dc.subjectSmad Signalingen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectPhysiological Processesen_US
dc.subjectAgingen_US
dc.subjectWomen's Healthen_US
dc.subjectOsteopenia and Osteoporosisen_US
dc.titleThe Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitorsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3454401en_US
dc.contributor.corporatenameDepartment of Pathology-
dc.contributor.corporatenameCollege of Graduate Studies-

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