Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis

Kastrinaki, Maria-Christina; Sidiropoulos, Prodromos; Roche, Stéphane; Ringe, Jochen; Lehmann, Sylvain; Kritikos, H; Vlahava, Virginia Maria; Delorme, Bruno; Eliopoulos, George D.; Jørgensen, Christian; Charbord, Pierre; Häupl, Thomas; Boumpas, Dimitrios T.; Papadaki, Helen Α.

doi:10.1136/ard.2007.076174

Cited by 144 publications

(135 citation statements)

References 36 publications

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“…MSCs have the potential to differentiate into multiple cell types, including osteogenic, adipogenic, and chondrogenic cell lineages and may contribute to tissue repair and regeneration. In chronic inflammatory bone disease, bone formation and regeneration are inhibited, which may be related to the inflammatory microenvironment and may affect MSC differentiation [5,6]. Human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs) have been isolated as multipotent stem cells that are capable of being used in stem cell-mediated therapies and tissue engineering [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

MiR-17 Modulates Osteogenic Differentiation Through a Coherent Feed-Forward Loop in Mesenchymal Stem Cells Isolated from Periodontal Ligaments of Patients with Periodontitis

et al. 2011

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Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, are the most common causes of bone tissue destruction. Recently, human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population of multipotent stem cells, have been used to reconstruct tissues destroyed by chronic inflammation. However, the impact of the local inflammatory microenvironment on tissue-specific stem cells and the mechanisms controlling the effects of the local inflammatory environment remain poorly understood. In this study, we found that the multidifferentiation potential of mesenchymal stem cells (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P-PDLSCs) was significantly lower than that of MSCs isolated from healthy human periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment resulted in an inhibition of miR-17 levels, and a perturbation in the expression of miR-17 partly reversed the differentiation potential of PDLSCs in this microenvironment. Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation. Western blotting and 3′ untranslated regions (3′-UTR) reporter assays confirmed that Smurf1 is a direct target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward loop. In this circuit, inflammatory cytokines led to direct activation of Smurf1 and downregulation of miR-17, thereby increasing degradation of Smurf1-mediated osteoblast-specific factors. The elucidation of the molecular mechanisms governing MSC osteogenic differentiation in a chronic inflammatory microenvironment could provide us with a better knowledge of chronic inflammatory disorder and improve stem cell-mediated inflammatory bone disease therapy.

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Section: Introductionmentioning

confidence: 99%

MiR-17 Modulates Osteogenic Differentiation Through a Coherent Feed-Forward Loop in Mesenchymal Stem Cells Isolated from Periodontal Ligaments of Patients with Periodontitis

et al. 2011

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“…To further characterize patients' PBMC relative telomere length as appropriate or inappropriate for a given age, we defined the observed/predicted relative telomere length ratio (O/P ratio) for each patient according to the equation derived from the linear regression analysis of the correlation between the PBMC relative telomere values and age (years) of the controls (y = -158.18x + 13813). 24 We found that the mean O/P telomere length ratio of the patients (0.73±0.32) was out of the 95% confidence limits (CI) of the healthy controls (mean O/P telomere length ratio 1.01 ±0.56, 95% CI 0.87 and 1.14) suggesting inappropriate telomere loss according to age in CIN patients ( Figure 1C). Overall, the mean telomere length of patient PBMCs was significantly lower than that expected on the basis of the age-adjusted healthy control distribution (6203.26±1871.90; P=0.0004).…”

Section: Telomere Length Analysis Of Pbmcs In Cin Patients and Healthmentioning

confidence: 96%

Abnormal telomere shortening of peripheral blood mononuclear cells and granulocytes in patients with chronic idiopathic neutropenia

Pavlaki

Kastrinaki²,

Klontzas³

et al. 2011

Haematologica

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BackgroundChronic idiopathic neutropenia is characterized by immune-mediated suppression of neutrophil production. Because patients with immune-mediated bone marrow failure syndromes display age-inappropriate telomere shortening in leukocytes, we investigated telomere lengths in peripheral blood mononuclear cells and granulocytes of patients with chronic idiopathic neutropenia. Design and MethodsWe studied 37 patients with chronic idiopathic neutropenia and 68 age-and sex-matched healthy controls. Relative telomere length and telomerase reverse transcriptase expression were assessed by a quantitative real time polymerase chain reaction. Telomerase activity was determined by a polymerase chain reaction-based immunoassay. ResultsThe mean relative telomere values of peripheral blood mononuclear cells and granulocytes were significantly lower in patients compared to controls, and significantly lower than expected on the basis of the age-adjusted healthy control distribution. The difference in the relative telomere lengths between patients and controls in both peripheral blood mononuclear cells and granulocytes was prominent in those under the age of 50 years. Contrary to the peripheral blood mononuclear cells, in which an inverse correlation was observed between relative telomere values and age, no significant correlation was noted between granulocyte telomere values and patient age. A significant correlation was observed between individual relative telomere values and absolute neutrophil counts. There was no difference in expression of telomerase reverse transcriptase in peripheral blood mononuclear cells between patients and controls but telomerase activity was identified at a significantly higher frequency in controls than in patients. No correlation was found between telomerase activity or telomerase reverse transcriptase expression and relative telomere lengths of peripheral blood mononuclear cells. ConclusionsPatients with chronic idiopathic neutropenia display age-inappropriate telomere shortening of peripheral blood cells and low telomerase activity in peripheral blood mononuclear cells. A compensatory increased proliferation of bone marrow hematopoietic progenitor cells in association with lymphocyte replicative exhaustion probably account for these abnormalities.

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“…Trypsinized MSCs from passage (P)-2 were induced to differentiate into adipocytes and osteoblasts as previously described [25,26]. Briefly, for the adipogenic differentiation, cells were cultured for 3 weeks in MSC medium supplemented with 10% FCS, 0.5 mM 1-methyl-3-butylisoxanthine, 1 mM dexamethasone, 0.2 mM indomethacin, and 10 mg/mL insulin.…”

Section: Msc Differentiation Assaysmentioning

confidence: 99%

“…MSC proliferative potential was evaluated by a Methyl Triazolyl Tetrazolium (MTT)-based assay in P2 cells and also by estimating the population doubling time through P2-P4 [26]. The formula 2 n = N x /N 0 was used for calculation of population doublings (n) at each passage based on the number of cells counted in the flask after trypsinization (N x ) and the number of cells initially plated (N 0 ).…”

Section: Proliferative Potential Of In Vitro Expanded Mscsmentioning

confidence: 99%

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Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

Pontikoglou

Kastrinaki²,

Klaus³

et al. 2013

Stem Cells and Development

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Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis

Abstract: In spite of some restrictions related to the impaired clonogenic and proliferative potential, our findings support the use of autologous BM MSCs in RA and may have important implications for the ongoing efforts to repair tissue injury commonly seen in the course of the disease.

Cited by 144 publications

References 36 publications

MiR-17 Modulates Osteogenic Differentiation Through a Coherent Feed-Forward Loop in Mesenchymal Stem Cells Isolated from Periodontal Ligaments of Patients with Periodontitis

MiR-17 Modulates Osteogenic Differentiation Through a Coherent Feed-Forward Loop in Mesenchymal Stem Cells Isolated from Periodontal Ligaments of Patients with Periodontitis

Abnormal telomere shortening of peripheral blood mononuclear cells and granulocytes in patients with chronic idiopathic neutropenia

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

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