Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by ectopic bone formation. The anti-inflammatory function of dipeptidyl peptidase-4 (DPP4) inhibitor has been reported in bone metabolism, but its utility in AS has not previously been investigated.
Methods: We assessed DPP4 level in serum, synovial fluid, and facet joint tissue of AS patients.
Spondyloarthritis (SpA) is a chronic inflammatory disease that leads to ankylosis of the axial skeleton. Celecoxib (cyclooxygenase-2 inhibitor, COX-2i) inhibited radiographic progression in a clinical study of SpA, but in the following study, diclofenac (COX-2 non-selective) failed to show that inhibition. Our study aimed to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited bone progression in SpA, and whether celecoxib had a unique function (independent of the COX-inhibitor), compared with the other NSAIDs.
View Article and Find Full Text PDFMany studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is responsible for ectopic new bone formation, but research on osteoclasts in ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclastmediated bone resorption in curdlan-injected SKG mice, a model that mimics AS. Compared to the Vehicle group, the Wnt5a treatment group exhibited statistically higher clinical arthritis scores and increased hindpaw thickness values.
View Article and Find Full Text PDFBackground: Complement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H's inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA).
View Article and Find Full Text PDFThis study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly.
View Article and Find Full Text PDFThe hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF.
View Article and Find Full Text PDFAnkylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood.
View Article and Find Full Text PDFSpondyloarthritis (SpA) is a chronic inflammatory disease that results in bone ankylosis. The tissue renin-angiotensin system (RAS) is an emerging pathway potentially implicated in SpA-associated bone changes. The aim of the present study was to determine the mechanisms underlying this relationship.
View Article and Find Full Text PDFAims: Muscle-bone interactions during fracture healing are rarely known. Here we investigated the presence and significance of myosin heavy chain 2 (MYH2), a component of myosin derived from muscles, in fracture healing.
Main Methods: We collected five hematoma and seven soft callus tissues from patients with distal radius fractures patients, randomly selected three of them, and performed a liquid chromatography-mass spectrometry (LC-MS) proteomics analysis.
Background: Human gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. Differential expression of Polycomb repressive complex 2 (PRC2) has been reported in various subtypes of glioma. However, the role of PRC2 in uncontrolled growth in glioma and its underlying molecular mechanisms remain to be elucidated.
View Article and Find Full Text PDFObjective: Bone morphogenetic protein receptor type 2 (BMPR2) has been associated with radiographic changes in ankylosing spondylitis (AS), but further characterization of the cellular signaling pathway in osteoprogenitor (OP) is not clearly understood. The aim of this study was to investigate the expression of BMPR2 and bone morphogenetic protein 2 (BMP2)-mediated responsibility in AS.
Methods: We collected 10 healthy control (HC) and 14 AS-OPs derived from facet joints.
Rheumatology (Oxford)
December 2023
Objectives: Th17 cells are known to play a significant role in AS. C-C motif chemokine ligand 20 (CCL20) binds to C-C chemokine receptor 6 (CCR6) on Th17 cells, promoting their migration to inflammation sites. The aim of this research is to examine the effectiveness of CCL20 inhibition in treating inflammation in AS.
View Article and Find Full Text PDFObjective: Ankylosing spondylitis (AS) exhibits paradoxical bone features typically characterized by new bone formation and systemic bone loss. Although abnormal kynurenine (Kyn), a tryptophan metabolite, has been closely linked to the disease activity of AS, the distinct role of its pathological bone features remains unknown.
Methods: Kynurenine sera level was collected from healthy control (HC; n = 22) and AS (n = 87) patients and measured by ELISA.
Objective: To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells.
Methods: This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor.
Protein phosphatase magnesium-dependent 1A (PPM1A), serine/threonine protein phosphatase, in sera level was increased in patients with ankylosing spondylitis (AS). Preosteoblasts were differentiated actively to matured osteoblasts by intracellular PPM1A overexpression. However, it was unclear whether extracellular PPM1A contributes to the excessive bone-forming activity in AS.
View Article and Find Full Text PDFObjectives: To identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS).
Methods: We newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).
Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC).
View Article and Find Full Text PDFAims: To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).
Methods: Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs.
Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation.
View Article and Find Full Text PDFBackground: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other.
Methods: We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses.
House dust mite (HDM) allergens cause inflammatory responses and chronic allergic diseases such as bronchial asthma and atopic dermatitis. Here, we investigate the mechanism by which HDM induces C-C chemokine ligand 20 (CCL20) expression to promote chronic inflammation and airway remodeling in an HDM-induced bronchial asthma mouse model. We showed that HDM increased CCL20 levels via the Akt-ERK1/2-C/EBPβ pathway.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2022