Objective: To determine whether HLA-B27 expression alters the response of bone marrow monocytes from HLA-B27/human β2 -microglobulin-transgenic (B27-Tg) rats to tumor necrosis factor α (TNFα) and, if so, whether this affects the cells involved in bone homeostasis.
Methods: Bone marrow monocytes were treated with RANKL or with TNFα to promote osteoclast formation. Osteoclasts were quantified by counting. Gene expression was measured using quantitative polymerase chain reaction analysis, and protein was detected by enzyme-linked immunosorbent assay, immunoblotting, or immunofluorescence. Effects of endogenously produced cytokines on osteoclast formation were determined with neutralizing antibodies.
Results: TNFα treatment enhanced osteoclast formation 2.5-fold in HLA-B27-expressing cells as compared to wild-type or to HLA-B7/human β2 -microglobulin-expressing monocytes. TNFα induced ∼4-fold up-regulation of HLA-B27, which was associated with the accumulation of misfolded heavy chains, binding of the endoplasmic reticulum (ER) chaperone BiP, and activation of an ER stress response, which was not seen with HLA-B7. No differences were seen with RANKL-induced osteoclastogenesis. Enhanced interleukin-1α (IL-1α) production from ER-stressed bone marrow monocytes from B27-Tg rats was found to be necessary and sufficient for enhanced osteoclast formation. However, bone marrow monocytes from B27-Tg rats also produced more interferon-β (IFNβ), which attenuated the effect of IL-1α on osteoclast formation.
Conclusion: HLA-B27-induced ER stress alters the response of bone marrow monocytes from B27-Tg rats to TNFα, which is associated with enhanced production of IL-1α and IFNβ, cytokines that exhibit opposing effects on osteoclast formation. The altered response of cells expressing HLA-B27 to proinflammatory cytokines suggests that this class I major histocompatibility complex allele may contribute to the pathogenesis of spondyloarthritis and its unique phenotype through downstream effects involving alterations in bone homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857096 | PMC |
| http://dx.doi.org/10.1002/art.38001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Commensurate Prior Model With Random Effects for Survival and Competing Risk Outcomes to Accommodate Historical Controls.
Pharm Stat
January 2025
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Clinical trials (CTs) often suffer from small sample sizes due to limited budgets and patient enrollment challenges. Using historical data for the CT data analysis may boost statistical power and reduce the required sample size. Existing methods on borrowing information from historical data with right-censored outcomes did not consider matching between historical data and CT data to reduce the heterogeneity.
View Article and Find Full Text PDFHypercholesterolemia triggers innate immune imbalance and transforms brain infarcts after ischemic stroke.
Front Immunol
January 2025
Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Post-stroke early activation of neutrophils contributes to intensive neuroinflammation and worsens disease outcomes. Other pre-existing patient conditions can modify the extent of their activation during disease, especially hypercholesterolemia. However, whether and how increased circulating cholesterol amounts can change neutrophil activation responses very early after stroke has not been studied.
View Article and Find Full Text PDFTherapeutic Potential of Different Injection Methods for Bone Marrow Mesenchymal Stem Cell Transplantation in Buslfan-Induced Male Rat Infertility.
J Stem Cells Regen Med
October 2024
Mansoura University, Faculty of Science, Zoology department, Mansoura, Dakahlia, Egypt.
In recent years, bone marrow derived mesenchymal stem cells (BM-derived MSCs) have emerged as a powerful cell-based therapy for various diseases, including male infertility. Demonstrating the efficiency of BM-derived MSCs transplantation by different routes of injection to home and repair testis of busulfan-induced azoospermic rats. In the present study, rat BM-derived MSC was isolated and characterized for mesenchymal &hematopoietic markers using flow-cytometry.
View Article and Find Full Text PDFEffects of different microfracture drilling parameters on bone quality: a finite element analysis.
Front Bioeng Biotechnol
January 2025
Department of Orthopaedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Background: Microfracture drilling is a surgical technique that involves creating multiple perforations in areas of cartilage defects to recruit stem cells from the bone marrow, thereby promoting cartilage regeneration in the knee joint. Increasing the exposed bone marrow surface area (more holes in the same area) can enhance stem cell outflow. However, when the exposed area is large, it may affect the mechanical strength of the bone at the site of the cartilage defect.
View Article and Find Full Text PDFViscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats.
Regen Biomater
November 2024
Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, PR China.
A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!