Journal ArticleDOI
BMP responsiveness in human mesenchymal stem cells.
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TLDR
The results suggest that BMP signaling in mesenchymal stem cells utilizes more than one system for transcriptional activation, suggesting that a defect exists in the system required for induction of the osteoblast phenotype.Abstract:
Bone morphogenetic proteins (BMPs) are well known to induce bone formation in animal models and can promote osteogenesis in cultures of multipotential mesenchymal stem cells (MSC) isolated from rat and mouse bone marrow. However, clinical trials of BMPs suggest that BMPs are relatively ineffective inducers of osteogenesis in humans. Recent studies from our lab indicate that when human bone marrow MSC are placed in primary culture, osteogenesis can be induced by dexamethasone (Dex), but not by BMP-2, -4, or -7. We have therefore investigated components of BMP signaling pathways in human MSC. First passage cells, derived from the bone marrow of patients undergoing hip replacement surgery, were cultured with ascorbate phosphate and treated with 100 nM dexamethasone (Dex), 100 ng/ml BMP, or both. After 6 days, alkaline phosphatase activity of cell extracts was measured, and RNA was extracted for RT-PCR analysis of mRNA levels. Among human MSC samples from more than a dozen patients, only one patient sample showed significantly elevated alkaline phosphatase after exposure to BMP; the rest responded to Dex but not BMP. Analysis of mRNA from cultured human MSC indicated that, while Dex treatment caused increased levels of mRNA for alkaline phosphatase, BMP did not. Noggin is a BMP-binding protein that is upregulated by BMPs. BMP-treated human MSC cultures that did not show increased alkaline phosphatase did express elevated levels of noggin mRNA, indicating that the cells are capable of some BMP response. Our results suggest that BMP signaling in mesenchymal stem cells utilizes more than one system for transcriptional activation. The inability of most human MSC to activate transcription of the alkaline phosphatase gene implies that a defect exists in the system required for induction of the osteoblast phenotype.read more
Citations
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Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.
TL;DR: Harnessing the migratory potential of MSCs by modulating their chemokine‐chemokine receptor interactions may be a powerful way to increase their ability to correct inherited disorders of mesenchymal tissues or facilitate tissue repair in vivo.
Journal ArticleDOI
Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells
Karri Mesimäki,Bettina Lindroos,Jyrki Törnwall,J. Mauno,Christian Lindqvist,Christian Lindqvist,Risto Kontio,Susanna Miettinen,Riitta Suuronen +8 more
TL;DR: This is the first clinical case where ectopic bone was produced using autoASCs in microvascular reconstruction surgery and it will pave way for new clinical trials in the field.
Journal ArticleDOI
Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation.
TL;DR: Understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.
Journal ArticleDOI
Non-hematopoietic bone marrow stem cells: Molecular control of expansion and differentiation
TL;DR: The first non-hematopoietic mesenchymal stem cells (MSCs) were discovered by Friedenstein in 1976 and it is demonstrated that multi-potent MSCs can be recovered from a variety of other adult tissues and differentiate into numerous tissue lineages including myoblasts, hepatocytes and possibly even neural tissue.
Journal ArticleDOI
Shear stress induces osteogenic differentiation of human mesenchymal stem cells.
TL;DR: It is demonstrated that shear stress stimulates hMSCs towards an osteoblastic phenotype in the absence of chemical induction, suggesting that certain mechanical stresses may serve as an alternative to chemical stimulation of stem cell differentiation.
References
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Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
TL;DR: Cloned cDNA encoding Osf2/Cbfa1 is identified as an osteoblast-specific transcription factor and as a regulator of osteoblasts differentiation.
Journal ArticleDOI
Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
Toshihisa Komori,Hideshi Yagi,Shintaro Nomura,Akira Yamaguchi,Koichi Sasaki,Kenji Deguchi,Y Shimizu,Roderick T. Bronson,Y.-H Gao,Masahiko Inada,Makoto Sato,R Okamoto,Yukihiko Kitamura,Shusaku Yoshiki,Tadamitsu Kishimoto +14 more
TL;DR: The data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.
Journal ArticleDOI
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Florian Otto,Anders P Thornell,Tessa Crompton,Angela Denzel,Kimberly C Gilmour,Ian R Rosewell,Gordon Stamp,Rosa S.P Beddington,Stefan Mundlos,Bjorn R. Olsen,Paul B. Selby,Michael John Owen +11 more
TL;DR: The Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the C bfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
Journal ArticleDOI
Transcriptional control by the TGF‐β/Smad signaling system
Joan Massagué,David Wotton +1 more
TL;DR: TGF‐β family members are multifunctional hormones, the nature of their effects depending on what has been called ‘the cellular context’ warrants mention at the outset.