MiR-181a Targets and Regulates Bone Morphogenetic Protein - WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells.

Mechanisms of WNT and bone morphogenetic protein (BMP) signaling crosstalk is in the focus of multiple biological studies, and it also has been discovered to play important roles in human mesenchymal stromal cells (MSC) that are of great interest for neocartilage engineering due to their high chondrogenic differentiation potential. However, MSC-derived chondrocytes undergo hypertrophic degeneration that impedes their clinical application for cartilage regeneration. In our previous study, we established that several microRNAs (miRs) are differentially expressed between articular chondrocytes (AC) - and MSC-derived neocartilage, with miR-181a being the most prominent candidate as key microRNA involved in the regulation of a balance between chondral and endochondral differentiation.

MicroRNA Signatures in Plasma of Patients With Venous Thrombosis: A Preliminary Report.

Background: Venous thromboembolism (VTE) is a frequent and potentially fatal disease, but its pathophysiology is incompletely understood. microRNAs (miR) dysregulate hemostatic proteins and influence thrombotic pathology by posttranscriptional regulation of gene expression. Consensus in defining VTE-related miR clusters and functionally relevant miR has not been reached.

MiR-218 affects hypertrophic differentiation of human mesenchymal stromal cells during chondrogenesis via targeting RUNX2, MEF2C, and COL10A1.

Background: Human mesenchymal stromal cells (MSC) hold hopes for cartilage regenerative therapy due to their chondrogenic differentiation potential. However, undesirable occurrence of calcification after ectopic transplantation, known as hypertrophic degeneration, remains the major obstacle limiting application of MSC in cartilage tissue regeneration approaches. There is growing evidence that microRNAs (miRs) play essential roles in post-transcriptional regulation of hypertrophic differentiation during chondrogenesis.

Differential expression of TGF-β superfamily members and role of Smad1/5/9-signalling in chondral versus endochondral chondrocyte differentiation.

Proteins of the transforming-growth-factor-β (TGF-β)-superfamily have a remarkable ability to induce cartilage and bone and the crosstalk of TGF-β - and BMP-signalling pathways appears crucial during chondrocyte development. Aim was to assess the regulation of TGF-β-superfamily members and of Smad2/3- and Smad1/5/9-signalling during endochondral in vitro chondrogenesis of mesenchymal stromal cells (MSC) relative to chondral redifferentiation of articular chondrocytes (AC) to adjust chondrocyte development of MSC towards a less hypertrophic phenotype. While MSC increased BMP4 and BMP7 and reduced TGFBR2 and TGFBR3-expression during chondrogenesis, an opposite regulation was observed during AC-redifferentiation.

Differential Regulation of SOX9 Protein During Chondrogenesis of Induced Pluripotent Stem Cells Versus Mesenchymal Stromal Cells: A Shortcoming for Cartilage Formation.

Induced pluripotent stem cells (iPSCs) are an attractive cell source for cartilage regeneration, but current in vitro chondrogenic differentiation protocols yield insufficient results. In search for shortcomings of iPSC chondrogenesis, this study investigated whether SOX9 protein was adequately regulated during multiphase chondrogenic differentiation of two human iPSC lines in a comparable manner like during mesenchymal stromal cell (MSC) chondrogenesis. Upon generation of intermediate mesenchymal progenitor cells (iMPCs), SOX9 was induced and reached variable protein levels compared to MSCs.

Quantification of Metanephrine and Normetanephrine in Urine Using Liquid Chromatography-Tandem Mass Spectrometry.

Measuring urinary metanephrines aides in the diagnosis of pheochromocytomas-catecholamine producing tumors. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allows for greater sensitivity and simpler sample preparation as compared with other techniques. Here we describe a simple LC-MS/MS method for measuring metanephrines in urine.

Stage-Specific miRs in Chondrocyte Maturation: Differentiation-Dependent and Hypertrophy-Related miR Clusters and the miR-181 Family.

Human mesenchymal stromal cells (hMSC) differentiating toward the chondrogenic lineage recapitulate successive phases of embryonic chondrocyte maturation developing from progenitor cells to hypertrophic chondrocytes. Osteoarthritic cartilage is characterized by an alteration in chondrocyte metabolism and upregulation of hypertrophic differentiation markers. A number of studies point toward a functional role for microRNAs (miRs) in controlling chondrocyte differentiation and development of osteoarthritis (OA).

A simple and robust LC-MS/MS method for measuring sirolimus and everolimus in whole blood.

Therapeutic drug monitoring of immunosuppressants sirolimus and everolimus is mandatory and liquid chromatography tandem mass spectrometry (LC-MS/MS) is the preferred technology for the measurement. Due to the high hydrophobicity these analytes bind to reverse-phase columns tightly and need column heating to elute. Column heating not only requires extra instrument preparation but also causes permanent column damage if the heater is left on while elution pumps stop by the end of the run.

Multicenter evaluation of the thermo scientific prelude for measurement of immunosuppressant drugs using sample preparation liquid chromatography-tandem mass spectrometry.

Immunosuppressant drugs (ISDs) are commonly prescribed to solid organ transplant patients. Their narrow therapeutic index and potential for toxicity necessitates careful monitoring of blood concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are increasingly used for ISD measurement.

Contribution of microRNA 24-3p and Erk1/2 to interleukin-6-mediated plasma cell survival.

Plasma cells can survive for long periods and continuously secrete protective antibodies, but plasma cell production of autoantibodies or transformation to tumor cells is detrimental. Plasma cell survival depends on exogenous factors from the surrounding microenvironment, and largely unknown intracellular mediators that regulate cell homeostasis. Here we investigated the contribution of the microRNA 24-3p (miR-24-3p) to the survival of human plasma cells under the influence of IL-6 and SDF-1α (stromal cell derived factor 1), both of which are bone marrow survival niche mediators.

Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry.

Methylmalonic acid (MMA) is a functional biomarker of vitamin B12 deficiency. Measurement of plasma MMA is challenging due to its small molecular weight and hydrophilic nature. Several liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed for measuring plasma MMA.

A simple liquid chromatography-tandem mass spectrometry method for measuring metanephrine and normetanephrine in urine.

Background: Measuring urinary fractionated metanephrines is one of the initial tests in the diagnosis of pheochromocytoma. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) represents the most specific and accurate technology for this purpose. The goal of this work was to develop a simple LC-MS/MS method for measuring metanephrines in urine.