Background: Low back pain (LBP) is one of the common musckloskeletal diseases and usual treated by epidural steroid injection (ESI). ESIs improve patients' quality of life, reduce lumbar radicular pain, and postpone spinal surgery. The mechanism of improvement is yet unscertain, perhaps involve type α collagen (COL2α) for bone maintenance, hence, we sought to investigate the role of injected steroids in bone healing focusing on the role of COL2α.Methods: All patients in this research were diagnosed by specialists based on their histories and clinical features and associated diseaeses or compiling therapy. Serum samples collected from LBP patients and control group for comparisons.Results: The present study found a significant (<0.0001) increase in the concentration of COL2α in patients with LBP after injection with ESI treatment compared with patients before injection and healthy individuals.Conclusion: ESI helps LBP sufferers by boosting COL2α, which repairs damaged tissues.

• MeSH
• Biomarkers analysis   MeSH
• Back Pain * drug therapy   MeSH
• Glucocorticoids administration & dosage   pharmacology   therapeutic use   MeSH
• Injections, Epidural * methods   MeSH
• Clinical Studies as Topic methods   MeSH
• Collagen Type II * administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Pain Management methods   MeSH
• Radiculopathy etiology   drug therapy   MeSH
• Bone Regeneration drug effects   MeSH
• Check Tag
• Humans MeSH

The authors discuss the current knowledge of Spondyloepiphyseal dysplasia with metatarsal short- ening (SED-MS), formerly Czech dysplasia based on literature sources and their own experience. This rare autosomal dominant (AD) skeletal disorder was first published as an original article entitled “Dominantly inherited progressive pseudorheumatoid dysplasia with hypoplastic toes” in Skeletal Radiology (2004) (authors: Ivo Mařík, Olga Maříková, Dana Zemková, Miloslav Kuklík, Kazimierz Kozlowski). SED-MS belongs to type II collagenopathies. This dysplasia is probably caused exclusively by the p.Arg275Cys (R275C, c.823C>T) mutation, which affects the integrity and stability of collagen fibrils. The COL2A1 mutational hot spot is thought to be unique among COL2A1 disorders. SED-MS occurs independently in all parts of the world (at least 13 families described). The main characteristic symp- toms are weather-dependent joint and spinal pain from early childhood, progressive arthropathy with early onset, platyspondyly, shortening of the 3 rd and 4 th metatarsals and in many cases sensori- neural hearing loss. Body height is normal, but arthropathy, which is often accompanied by synovial osteochondromatosis, leads to pain and limitation of movement and early disability. The principal differential diagnosis includes Albright’s hereditary osteodystrophy, Brachydactyly E, Idiopathic juvenile osteoarthritis, Progressive pseudorheumatoid dysplasia, and other type II collagenopathies, specifically Osteoarthritis with mild chondrodysplasia (OMIM 604864), Spondyloperipheral dysplasia (OMIM 271700) and Stanescu type of Spondyloepiphyseal dysplasia (OMIM 616583). The main aim of the authors is to present recent literature findings on SED-MS with a focus on the evolution of characteristic clinical findings and radiological features and orthopaedic treatment options based on the experience with a Czech family (AD transmission in five generations) originally published in Skeletal Radiology in 2004 and other literature data. The second objective deals with the differential diagnosis of type II collagenopathies, specifically comparing patients with the p.Arg275Cys mutation with patients who were previously diagnosed with Czech dysplasia and in whom this mutation was not identified. The two cases presented pro- vide evidence that there is phenotypic overlap between Czech dysplasia and mild forms of spondy- loperipheral dysplasia. Czech dysplasia overlaps with Early-onset osteoarthritis (EO-OA) with mild chondrodysplasia.

• MeSH
• Collagen Type II MeSH
• Bone Density MeSH
• Humans MeSH
• Metatarsal Bones abnormalities   pathology   MeSH
• Mutation MeSH
• Bone Diseases MeSH
• Connective Tissue Diseases MeSH
• Osteochondrodysplasias * diagnosis   genetics   therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.

• MeSH
• Arthritis genetics   MeSH
• Child MeSH
• Adult MeSH
• Phenotype MeSH
• Infant MeSH
• Collagen Type II genetics   MeSH
• Collagen Type XI genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• DNA Mutational Analysis MeSH
• Connective Tissue Diseases genetics   MeSH
• Retinal Detachment genetics   MeSH
• Hearing Loss, Sensorineural genetics   MeSH
• Child, Preschool MeSH
• Pedigree MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.

• MeSH
• Spondylitis, Ankylosing blood   diagnosis   MeSH
• Biomarkers blood   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Fibrillar Collagens metabolism   MeSH
• Collagen Type II metabolism   MeSH
• Collagen Type III metabolism   MeSH
• Collagen Type I metabolism   MeSH
• Collagen Type IV metabolism   MeSH
• Humans MeSH
• Spondylarthritis blood   diagnosis   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In the present work, we developed a novel needleless emulsion electrospinning technique that improves the production rate of the core/shell production process. The nanofibres are based on poly-ε-caprolactone (PCL) as a continuous phase combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68 nanofibres show a time-regulated release of active molecules. Needleless emulsion electrospinning was used to encapsulate a diverse set of compounds to the core phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming growth factor-β and basic fibroblast growth factor]. In addition, the PF-68 facilitates the preservation of the bioactivity of delivered proteins. The system's potential was highlighted by an improvement in the metabolic activity and proliferation of mesenchymal stem cells. The developed system has the potential to deliver susceptible molecules in tissue-engineering applications.

• MeSH
• Biocompatible Materials pharmacology   MeSH
• Dextrans chemistry   MeSH
• Emulsions chemistry   MeSH
• Needles MeSH
• Collagen Type II metabolism   MeSH
• Horseradish Peroxidase metabolism   MeSH
• Mesenchymal Stem Cells cytology   drug effects   metabolism   MeSH
• Intercellular Signaling Peptides and Proteins pharmacology   MeSH
• Swine, Miniature MeSH
• Nanofibers chemistry   ultrastructure   MeSH
• Poloxamer chemistry   MeSH
• Polyesters chemistry   MeSH
• Swine MeSH
• Proteins administration & dosage   MeSH
• Rhodamines chemistry   MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds chemistry   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

• MeSH
• Chondrocytes cytology   drug effects   metabolism   MeSH
• Olfactory Mucosa cytology   drug effects   growth & development   metabolism   MeSH
• Embryo, Mammalian MeSH
• Homeodomain Proteins genetics   metabolism   MeSH
• Integrases genetics   metabolism   MeSH
• Collagen Type II genetics   metabolism   MeSH
• Humans MeSH
• Maxillofacial Development genetics   MeSH
• Morphogenesis drug effects   genetics   MeSH
• Brain drug effects   growth & development   metabolism   MeSH
• Mutagens administration & dosage   MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Nasal Cartilages cytology   drug effects   growth & development   metabolism   MeSH
• Face anatomy & histology   embryology   MeSH
• Facial Bones cytology   drug effects   growth & development   metabolism   MeSH
• Hedgehog Proteins genetics   metabolism   MeSH
• Recombinant Fusion Proteins genetics   metabolism   MeSH
• Signal Transduction * MeSH
• Tamoxifen administration & dosage   MeSH
• Transcription Factors genetics   metabolism   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: Bioactive peptides derived from receptor binding motifs of native proteins are a potent source of bioactive molecules that can induce signalling pathways. These peptides could substitute for osteogenesis promoting supplements. The work presented here compares three kinds of bioactive peptides derived from collagen III, bone morphogenetic protein 7 (BMP-7) and BMP-2 with their potential osteogenic activity on the model of porcine mesenchymal stem cells (pMSCs). MATERIALS AND METHODS: pMSCs were cultured on electrospun polycaprolactone nanofibrous scaffolds with different concentrations of the bioactive peptides without addition of any osteogenic supplement. Analysis of pMSCs cultures included measurement of the metabolic activity and proliferation, immunofluorescence staining and also qPCR. RESULTS: Results showed no detrimental effect of the bioactive peptides to cultured pMSCs. Based on qPCR analysis, the bioactive peptides are specific for osteogenic differentiation with no detectable expression of collagen II. Our results further indicate that peptide derived from BMP-2 protein promoted the expression of mRNA for osteocalcin (OCN) and collagen I significantly compared to control groups and also supported deposition of OCN as observed by immunostaining method. CONCLUSION: The data suggest that bioactive peptide with an amino acid sequence of KIPKASSVPTELSAISTLYL derived from BMP-2 protein was the most potent for triggering osteogenic differentiation of pMSCs.

• MeSH
• Cell Differentiation drug effects   MeSH
• Cell Culture Techniques MeSH
• Collagen Type II genetics   metabolism   MeSH
• Collagen Type I genetics   metabolism   MeSH
• Microscopy, Confocal MeSH
• Cells, Cultured MeSH
• Mesenchymal Stem Cells cytology   drug effects   metabolism   MeSH
• Microscopy, Electron, Scanning MeSH
• Swine, Miniature MeSH
• Osteogenesis drug effects   MeSH
• Osteocalcin genetics   metabolism   MeSH
• Peptides chemistry   pharmacology   MeSH
• Swine MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The aim of this study was to assess the efficacy of choline-stabilized orthosilicic acid (ch-OSA) in patients with symptomatic knee osteoarthritis (OA). METHODS: In a multicenter, double-blind, placebo-controlled study, 211 patients with knee OA (Kellgren and Lawrence grade II or III) and moderate to moderately severe pain were randomly allocated to ch-OSA or placebo for 12 weeks. The primary outcome was the change in the WOMAC pain subscale from baseline to week 12. Secondary outcomes were changes from baseline to week 12 in WOMAC total, WOMAC stiffness, WOMAC physical function, Subject Global Assessment and levels of cartilage degradation biomarkers C-terminal telopeptide of collagen type II (CTX-II) and cartilage oligomeric matrix protein (COMP). Pre-specified subgroup analyses included the effect of gender. RESULTS: A total of 166 (120 women, 46 men) patients were included in the analysis (87 and 79 in the ch-OSA and placebo group, respectively). In the total study population, no differences were observed between the two treatment groups for the different outcomes but significant treatment x gender interactions were found. In men taking ch-OSA, a significant improvement in WOMAC total, WOMAC stiffness and WOMAC physical function as well as a lower increase in biomarker levels of cartilage degradation was observed, but not in women. The change in WOMAC pain showed a similar positive trend in men taking ch-OSA. CONCLUSION: After 12 weeks of treatment, no effect was found of ch-OSA in the total study population on clinical parameters and biomarkers, but a gender interaction was observed. In men, ch-OSA was found effective in reducing symptoms of knee OA, which was associated with a slight but significant reduction of biomarkers that are related to cartilage degradation. TRIAL REGISTRATION: The study was registered retrospectively: ISRCTN88583133 . Registration date: 2015-10-07.

• MeSH
• Administration, Oral MeSH
• Osteoarthritis, Knee drug therapy   MeSH
• Biomarkers analysis   MeSH
• Choline administration & dosage   therapeutic use   MeSH
• Cartilage pathology   MeSH
• Cartilage Oligomeric Matrix Protein analysis   MeSH
• Double-Blind Method MeSH
• Collagen Type II analysis   MeSH
• Silicic Acid administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Pain Management methods   MeSH
• Pain Measurement MeSH
• Aged MeSH
• Sex Factors MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Protilátky namířené proti různým autoantigenům představují heterogenní skupinu imunoglobulinů, které se liší kvalitativními i kvantitativními vlastnostmi. Důležitou kvalitativní charakteristikou protilátek je jejich afinita/avidita, která se mění v procesu jejího vyzrávání během imunitní odpovědi. Cílem studie bylo shrnutí znalostí o aviditě vybraných autoprotilátek u určitých autoimunitních onemocnění. Avidita různých autoprotilátek se liší za různých klinických situací. V biologických tekutinách pacientů s autoimunitními onemocnění se vyskytují protilátky s nízkou, střední i s vysokou hodnotou avidity. U autoimunitních chorob nemusí být proces vyzrávání avidity spojen s progresí od nízkých k vyšším hodnotám tak, jak je to typické pro protilátky proti exogenním antigenům. Avidita každé autoprotilátky by proto měla být posuzována individuálně. Některé studie naznačují možný přínos stanovení avidity pro upřesnění diagnózy a prognózy vybraných autoimunitních onemocnění.

Autoantibodies directed against various self-antigens comprise a heterogeneous group of immunoglobulins, which differ in their qualitative and quantitative features. An important qualitative characteristic of antibodies is affinity/avidity, which changes in the process of its maturation during the immune response. This study is aimed to summarize the knowledge about avidity of selected autoantibodies in certain autoimmune diseases. The avidity of various autoantibodies differs under distinct clinical situations. High-, moderate or low-avidity may be found in biological fluids in patients with autoimmune diseases. The avidity maturation associated with progression from low to high values typical for antibodies against exogenous antigens is not always uniform in autoimmune diseases; therefore, the avidity of each autoantibody should be judged individually. Some studies promise the possible benefit of avidity examination for the refinement of diagnosis and prediction of selected autoimmune diseases.

• Keywords
• anti-GBM, onkoneuronální protilátky, anti-Hu, anti-Yo, protilátky proti glomerulární bazální membráně,
• MeSH
• Antibody Affinity * immunology   MeSH
• Alzheimer Disease immunology   blood   MeSH
• Amyloid beta-Peptides immunology   blood   MeSH
• Anti-Glomerular Basement Membrane Disease immunology   blood   MeSH
• Autoantigens immunology   MeSH
• Autoantibodies * immunology   blood   MeSH
• Celiac Disease immunology   blood   MeSH
• Citrulline immunology   blood   MeSH
• Diabetes Mellitus, Type 1 immunology   blood   MeSH
• Glutamate Decarboxylase immunology   blood   MeSH
• Insulin Antibodies immunology   blood   MeSH
• Arthritis, Juvenile immunology   blood   MeSH
• Collagen Type II immunology   blood   MeSH
• Humans MeSH
• Disease Susceptibility * immunology   MeSH
• Neoplasms immunology   blood   MeSH
• Prediabetic State immunology   blood   MeSH
• Nerve Tissue Proteins immunology   blood   MeSH
• Antibodies, Neoplasm immunology   blood   MeSH
• Arthritis, Rheumatoid immunology   blood   MeSH
• Transglutaminases immunology   blood   MeSH
• Receptor-Like Protein Tyrosine Phosphatases, Class 8 immunology   blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, a potent immunosuppressive pathway, is a promising approach for treatment of RA. Extracellular adenosine can come from two sources: transport of intracellular adenosine and hydrolysis of extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility of CD73-deficient C57BL/6 mice to collagen-induced arthritis (CIA), a well-established mouse model of RA. Our data demonstrated that CD73-deficient mice are significantly more susceptible to CIA than wild-type mice. CD73 deficiency resulted in an increased production of proinflammatory cytokines in the joints, increased Th1 T cell responses, and increased joint destruction. Surprisingly, this was accompanied by delayed anticollagen IgG responses, suggesting defective isotype class switching in CD73-deficient mice. Using bone marrow chimera mice, we demonstrated that CD73 expression on nonhematopoietic cells, but not on hematopoietic cells, was important for protection from CIA. We further demonstrated that administration of a selective A2A adenosine receptor agonist to CD73-deficient mice resulted in arthritis incidence similar to wild-type mice in support of a protective role for A2A signaling. Taken together, our study identifies CD73 as an important regulator of CIA in mice. It also strengthens the notion that CD73-generated adenosine by nonhematopoietic cells plays a protective role in RA and suggests that strategies able to enhance CD73 activity or expression levels may be a valid therapeutic option.

• MeSH
• 5'-Nucleotidase deficiency   genetics   immunology   MeSH
• Adenosine analogs & derivatives   pharmacology   MeSH
• Adenosine A2 Receptor Agonists pharmacology   MeSH
• Arthritis, Experimental genetics   immunology   prevention & control   MeSH
• CD4-Positive T-Lymphocytes immunology   metabolism   MeSH
• Cytokines immunology   metabolism   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Phenethylamines pharmacology   MeSH
• Immunoglobulin G immunology   MeSH
• Interferon-gamma immunology   metabolism   MeSH
• Joints immunology   metabolism   pathology   MeSH
• Collagen Type II immunology   MeSH
• Chickens MeSH
• Lymph Nodes immunology   metabolism   MeSH
• Inflammation Mediators immunology   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Disease Susceptibility immunology   MeSH
• Disease Resistance genetics   immunology   MeSH
• Avian Proteins immunology   MeSH
• Th1 Cells immunology   metabolism   MeSH
• Bone Marrow Transplantation MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH