The pluripotent mesenchymal stem cells give rise to osteoblasts, adipocytes, chondrocytes, and myoblasts. The differentiation of these stem cells into each of the mature functional cells may be controlled by a distinctive master gene(s) and is associated with temporal and spatial expression of diverse genes. Identification of genes that are expressed during the differentiation of the mesenchymal cells to osteoblasts is, therefore, important to obtain insights into the molecular mechanisms of osteogenesis. The murine undifferentiated mesenchymal cell 3T3-F442A, when treated with the bone morphogenetic protein 2 (BMP-2), a well-characterized inducer of mesenchymal cell differentiation, exhibited both osteoblastic and adipocytic differentiation. Using the SAGE (serial analysis of gene expression) technique, which has been shown to enable quantitative analysis of large numbers of genes in a simple and quick manner, we obtained 1600 sequence tags representing 2107 individual nucleotide sequences from control and BMP-2-treated 3T3-F442A cells, respectively. By comparing the frequency of tag occurrence, we found profiles of up- or downregulated genes associated with osteoblast or adipocyte phenotype such as type I collagen, osteonectin and OSF-2, or C/EBPbeta, aP2, fatty acid synthase, and lipoprotein lipase, respectively, in BMP-2-treated 3T3-F442A cells. Our data show that BMP-2 induces not only osteoblastic but also adipocytic differentiation in the 3T3-F442A cells. They also show that the 3T3-F442A cells have bipotentials of differentiating toward osteoblasts and adipocytes. The results, therefore, might explain the inverse correlation between trabecular bone volume and fat volume in the bone marrow cavity. The results also suggest that the SAGE may be a useful technique that allows us a fast and efficient way to generate global and local views of gene expression associated with cellular differentiation of the mesenchymal stem cells.
Background
The diagnosis of persistent infection before reimplantation in two-stage exchange arthroplasty for periprosthetic joint infection (PJI) remains challenging. Currently, several studies suggested coagulation-related markers, such as D-dimer and fibrinogen, may be promising in diagnose of PJI. The purpose of the study was to investigate the predictive values of plasma D-dimer and fibrinogen for assessment of persistent infection before reimplantation hip arthroplasty.
Methods
We retrospectively reviewed 129 hips that treated with two-stage exchange arthroplasty for PJI from 2012 to 2016 in our institution. The persistent infection before reimplantation was based on a modified Musculoskeletal Infection Society (MSIS) criteria. After exclusion, 102 hips were included in the final analysis. Receiver operating characteristic (ROC) curves were generated to determine the prognostic value of plasma D-dimer and fibrinogen in predicting persistent infection before reimplantation.
Results
The area the under ROC curves (AUC) for fibrinogen (0.773; 95% confidential interval [CI], 0.569–0.905) was significantly higher than that of D-dimer (0.565; 95% CI, 0.329–0.777). With the calculated threshold of fibrinogen set at 3.61 g/L, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was 87.5%, 62.8%, 16.7%, and 98.3%, respectively. With the threshold value of D-dimer set at 0.82 μg/mL, the sensitivity, specificity, PPV, and NPV was 83.3%, 41.9%, 21.7%, and 92.9%, respectively.
Conclusions
In conclusion, the current study reveals that the plasma fibrinogen may be a promising biomarker in predicting persistent infection before reimplantation. Further prospective studies with larger cohorts are needed to validate predictive values and optimal thresholds of coagulation-related markers.
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