PloS one, 2015-12, Vol.10 (12), p.e0144655-e0144655
2015
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis
- Ist Teil von
- PloS one, 2015-12, Vol.10 (12), p.e0144655-e0144655
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0144655Titel-ID: cdi_plos_journals_1749591869
- Format
- –
- Schlagworte
- Adult, Ankylosing spondylitis, Anti-Inflammatory Agents, Non-Steroidal - therapeutic use, Antibodies, Monoclonal - therapeutic use, Antirheumatic Agents - therapeutic use, Axial skeleton, B-Lymphocytes - immunology, B-Lymphocytes - metabolism, Biocompatibility, Biomarkers, Biomedical materials, Bone growth, Bone loss, Bone Resorption, Bone turnover, Care and treatment, CC chemokine receptors, CCR2 protein, Cytokines, Cytokines - blood, Diagnosis, Differentiation, Female, Flow cytometry, Gene expression, Gene Expression Profiling, Hospitals, Humans, Immunophenotyping, Inflammation, Inflammation Mediators - blood, Inflammatory diseases, Interleukin 23, L-selectin, Leukocytes, Ligands, Lymphocytes, Lymphocytes B, Lymphocytes T, Male, Metabolic disorders, Middle Aged, Molecular Targeted Therapy, Monocyte chemoattractant protein 1, Necrosis, NMR, Nuclear magnetic resonance, Osteoclastogenesis, Osteoclasts, Osteoclasts (Biology), Osteoclasts - drug effects, Osteoclasts - metabolism, Osteogenesis, Osteoporosis, Osteoprogenitor cells, Patients, Phenotype, Physicians, Precursors, RANK Ligand - metabolism, Rheumatology, Risk factors, Serum levels, Skeleton, Spondylitis, Spondylitis, Ankylosing - drug therapy, Spondylitis, Ankylosing - immunology, Spondylitis, Ankylosing - metabolism, Spondylitis, Ankylosing - pathology, Stimuli, Subpopulations, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, Therapy, TRANCE protein, Tumor necrosis factor, Tumor necrosis factor inhibitors, Tumor necrosis factor-TNF, Tumor Necrosis Factors - antagonists & inhibitors