scholarly journals The effect of sword bean extract on the relationship between rheumatoid arthritis and periodontitis in mice

2019 ◽  
Author(s):  
Kosei Matsumoto ◽  
Yuko Nakatsuka ◽  
Kaname Shirai ◽  
Shintaro Shimizu ◽  
Shunshuke Yanase ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
Cathepsin K ◽  
Joint Inflammation ◽  
Tissue Destruction ◽  
Tissue Inflammation ◽  
Canavalia Gladiata ◽  
Experimental Mouse ◽  
The Relationship

AbstractObjectivesSeveral studies in humans and experimental animals have reported an interaction between rheumatoid arthritis (RA) and periodontitis (PD). We previously showed that extracts of Canavalia gladiata (sword bean extract, SBE) can treat PD in rats. Here, we investigated the relationship between RA and PD and the effects of SBE in an experimental mouse model.MethodsFemale SKG mice were assigned to eight groups (n=6/group): (1) Untreated controls, (2) RA (induced at 6 weeks of age), (3) PD (induced at 10 weeks of age), (4) RA + PD, (5) SBE (2 mg/ml in drinking water starting at 5 weeks of age), (6) PD + SBE, (7) RA + SBE, and (8) RA + PD + SBE. Mice were sacrificed at 13 weeks of age, and alveolar bone resorption, periodontal tissue inflammation, and paw joint inflammation were assessed by histology and immunohistochemistry.ResultsMice in the RA + PD group exhibited significantly higher inflammation scores in the joint tissues as well as more abundant IL-17-positive cells and cathepsin K-positive osteoclasts in the radial bone compared with the RA mice. Alveolar bone resorption was also significantly more severe in the RA + PD mice than in the PD mice. SBE treatment significantly improved all bone resorption and tissue inflammation scores in mice with RA + PD.ConclusionConcomitant RA and PD exacerbates the tissue destruction symptomatic of each condition. SBE suppresses all parameters evaluated, suggesting that it is has anti-inflammatory activities in both RA and PD.

scholarly journals Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5324
Author(s):  
In Seol Yoo ◽  
Yu-Ran Lee ◽  
Seong Wook Kang ◽  
Jinhyun Kim ◽  
Hee-Kyoung Joo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Joint Inflammation ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Control ◽  
The Relationship

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

scholarly journals Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin

1998 ◽  
Vol 66 (9) ◽  
pp. 4158-4162 ◽  
Author(s):  
Yuval Zubery ◽  
Colin R. Dunstan ◽  
Beryl M. Story ◽  
Lakshmyya Kesavalu ◽  
Jeffrey L. Ebersole ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Tissue Injury ◽  
Bone Destruction ◽  
Fusobacterium Nucleatum ◽  
Host Responses ◽  
Periodontal Pathogens ◽  
Tissue Destruction

ABSTRACT Gingival inflammation, bacterial infection, alveolar bone destruction, and subsequent tooth loss are characteristic features of periodontal disease, but the precise mechanisms of bone loss are poorly understood. Most animal models of the disease require injury to gingival tissues or teeth, and the effects of microorganisms are thus complicated by host responses to tissue destruction. To determine whether three putative periodontal pathogens, Porphyromonas gingivalis, Campylobacter rectus, andFusobacterium nucleatum, could cause localized bone resorption in vivo in the absence of tissue injury, we injected live or heat-killed preparations of these microorganisms into the subcutaneous tissues overlying the calvaria of normal mice once daily for 6 days and then examined the bones histologically. We found that all three microorganisms (both live and heat killed) stimulated bone resorption and that the strain of F. nucleatum used appeared to be the strongest inducer of osteoclast activity. Treatment of the mice concomitantly with indomethacin reduced but did not completely inhibit bone resorption by these microorganisms, suggesting that their effects were mediated, in part, by arachidonic acid metabolites (e.g., prostaglandins). Our findings indicate that these potential pathogens can stimulate bone resorption locally when placed beside a bone surface in vivo in the absence of prior tissue injury and support a role for them in the pathogenesis of bone loss around teeth in periodontitis.

scholarly journals The role of RANK ligand/osteoprotegerin in rheumatoid arthritis

2012 ◽  
Vol 4 (4) ◽  
pp. 225-233 ◽  
Author(s):  
Piet Geusens
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Destruction ◽  
Joint Inflammation ◽  
Nuclear Factor Κb ◽  
Coupling Factor ◽  
Essential Components ◽  
Bone Edema ◽  
Magnetic Resonance Imaging Mri

In the complex system of bone remodeling, the receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) pathway is the coupling factor between bone formation and bone resorption. RANKL binds to the RANK receptor of pre-osteoclasts and mature osteoclasts and stimulates their activation and differentiation. The production of RANKL/OPG by osteoblasts is influenced by hormones, growth factors and cytokines, which each have a different effect on the production of RANKL and OPG. Ultimately, the balance between RANKL and OPG determines the degree of proliferation and activity of the osteoclasts. In rheumatoid arthritis (RA), bone erosions are the result of osteoclastic bone resorption at the sites of synovitis, where RANKL expression is also found. Furthermore, magnetic resonance imaging (MRI) bone edema in RA indicates the presence of active inflammation within bone and the presence of osteitis, which is also associated with the expression of RANKL. Bone loss has been documented in the cortical and trabecular bone in the joints of the hand of RA patients. Both synovitis and periarticular bone involvement (osteitis and bone loss) are essential components of RA: they occur early in the disease and both are predictive for the occurrence and progression of bone damage. RANKL knockout mice and mice treated with OPG did not develop focal bone loss, in spite of persistent joint inflammation. Inhibition of osteoclasts by denosumab, a humanized antibody that selectively binds RANKL, has revealed in patients with RA that the occurrence of erosions and periarticular bone loss can be halted, however without affecting synovial inflammation. This disconnect between inflammation and bone destruction opens new ways to separately focus treatment on inflammation and osteoclastogenesis for preventing and/or minimizing the connection between joints and subchondral bone and bone marrow.

scholarly journals P130 The relationship between antinuclear antibodies and erosive disease in patients with rheumatoid arthritis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Thushyanthan Guruparan ◽  
Matthew Hutchinson ◽  
Rhys Hayward ◽  
Henry Penn ◽  
Parul Kalia
Keyword(s):  
Rheumatoid Arthritis ◽  
Antinuclear Antibodies ◽  
Joint Inflammation ◽  
X Rays ◽  
Erosive Disease ◽  
Positive Group ◽  
Number Of Patients ◽  
Group 2 ◽  
The Relationship ◽  
Group 1

Abstract Background/Aims  The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients. Methods  This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups. Results  Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p &lt; 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091). Conclusion  Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship. Disclosure  T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.

scholarly journals Single Cell Transcriptomics and Flow Cytometry Reveal Disease-associated Fibroblast Subsets in Rheumatoid Arthritis

2017 ◽  
Author(s):  
Fumitaka Mizoguchi ◽  
Kamil Slowikowski ◽  
Jennifer L Marshall ◽  
Kevin Wei ◽  
Deepak A Rao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Cell ◽  
Surface Protein ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
Matrix Remodeling ◽  
Tissue Destruction ◽  
Transcriptomics Data ◽  
Synovial Tissues ◽  
Tissue Matrix

AbstractFibroblasts mediate normal tissue matrix remodeling, but they can cause fibrosis or tissue destruction following chronic inflammation. In rheumatoid arthritis (RA), synovial fibroblasts expand, degrade cartilage, and drive joint inflammation. Little is known about fibroblast heterogeneity or if aberrations in fibroblast subsets relate to disease pathology. Here, we used an integrative strategy, including bulk transcriptomics on targeted subpopulations and unbiased single-cell transcriptomics, to analyze fibroblasts from synovial tissues. We identify 7 phenotypic fibroblast subsets with distinct surface protein phenotypes, and these collapsed into 3 subsets based on transcriptomics data. One subset expressing PDPN, THY1, but lacking CD34 was 3-fold expanded in RA relative to osteoarthritis (P=0.007); most of these cells expressed CDH11. The subsets were found to differ in expression of cytokines and matrix metalloproteinases, localization in synovial microanatomy, and in response to TNF. Our approach provides a template to identify pathogenic stromal cellular subsets in complex diseases.

scholarly journals Bone innervation and vascularization regulated by osteoclasts contribute to refractive pain-related behavior in the collagen antibody-induced arthritis model

2021 ◽  
Author(s):  
Resti Rudjito ◽  
Nilesh Agalave ◽  
Alex Bersellini Farinotti ◽  
Azar Baharpoor ◽  
Arisai Martinez Martinez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Late Phase ◽  
Cathepsin K ◽  
Neutralizing Antibody ◽  
Mechanical Hypersensitivity ◽  
Inflammatory Phase ◽  
Local Bone ◽  
Underlying Mechanisms ◽  
Bone Vascularization

Objective: Rheumatoid arthritis is often characterized by eroded joints and chronic pain that outlasts disease activity. Whilst several reports show strong associations between bone resorption and nociception, the underlying mechanisms remain to be unraveled. Here, we used the collagen antibody-induced arthritis (CAIA) model to examine the contribution of osteoclasts in pain regulation. The antinociceptive effects of osteoclasts inhibitors and their mechanisms of actions involving bone vascularization and innervation were also explored. Methods: BALB/c female mice were subjected to CAIA by intravenous injection of a collagen type-II antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Degree of arthritis, bone resorption, mechanical hypersensitivity, vascularization and innervation in the ankle joint were assessed. Animals were treated with osteoclast inhibitors, zoledronate and cathepsin K inhibitor (T06), and netrin-1 neutralizing antibody. Potential pronociceptive factors were examined in primary osteoclast cultures. Results: CAIA induced local bone loss in the calcaneus with ongoing increased osteoclast activity during the inflammatory phase of the model, but not after inflammation has resolved. Mechanical hypersensitivity was reversed by zoledronate in late but not inflammatory phase CAIA. This effect was coupled to the ability of osteoclasts to modulate bone vascularization and innervation, which was inhibited by osteoclast inhibitors. CAIA-induced hypersensitivity in the late phase was also reversed by anti-netrin-1 antibody. Conclusion: Osteoclasts induce pain-like behavior in the CAIA model independent of inflammation via effects on bone vascularization and innervation. Keywords: pain, rheumatoid arthritis, osteoclast, vascularization, innervation

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