Faculty Opinions recommendation of Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis.

2009 ◽  
Author(s):  
Mark Johnson ◽  
Cielo Barragan
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Osteoblast Function

Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S158
Author(s):  
N.C. Walsh ◽  
S. Reinwald ◽  
C.A. Manning ◽  
K.W. Condon ◽  
K. Iwata ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Osteoblast Function

Osteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis

2009 ◽  
Vol 24 (9) ◽  
pp. 1572-1585 ◽  
Author(s):  
Nicole C Walsh ◽  
Susan Reinwald ◽  
Catherine A Manning ◽  
Keith W Condon ◽  
Ken Iwata ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Osteoblast Function

scholarly journals Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression

2016 ◽  
Vol 76 (3) ◽  
pp. 612-619 ◽  
Author(s):  
E A Ross ◽  
A J Naylor ◽  
J D O'Neil ◽  
T Crowley ◽  
M L Ridley ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Bone Erosion ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Critical Determinant ◽  
Anti Inflammatory

ObjectivesTristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP.MethodsThe expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP.ResultsTTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation.ConclusionsThe phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.

scholarly journals Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuyue Zuo ◽  
Guo-Min Deng
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Therapeutic Targets ◽  
Bone Destruction ◽  
Signaling Molecules ◽  
Fc Gamma Receptors ◽  
Dual Roles ◽  
Signaling Transduction

Bone erosion is one of the primary features of inflammatory arthritis and is caused by excessive differentiation and activation of osteoclasts. Fc gamma receptors (FcγRs) have been implicated in osteoclastogenesis. Our recent studies demonstrate that joint-deposited lupus IgG inhibited RANKL-induced osteoclastogenesis. FcγRI is required for RANKL-induced osteoclastogenesis and lupus IgG-induced signaling transduction. We reviewed the results of studies that analyzed the association between FcγRs and bone erosion in inflammatory arthritis. The analysis revealed the dual roles of FcγRs in bone destruction in inflammatory arthritis. Thus, IgG/FcγR signaling molecules may serve as potential therapeutic targets against bone erosion.

scholarly journals Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis

2013 ◽  
Vol 74 (1) ◽  
pp. 196-203 ◽  
Author(s):  
D A Binks ◽  
E M Gravallese ◽  
D Bergin ◽  
R J Hodgson ◽  
A L Tan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Subchondral Bone ◽  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Cruciate Ligament ◽  
Vascular Anatomy ◽  
Cyst Formation ◽  
Cruciate Ligaments ◽  
Bone Damage ◽  
Vascular Channels

ObjectivesThe purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA).MethodsNormal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion.ResultsVascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%).ConclusionThe findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

Circulating Dickkopf-1 and Radiological Progression in Patients with Early Rheumatoid Arthritis Treated with Etanercept

2008 ◽  
Vol 35 (12) ◽  
pp. 2313-2315 ◽  
Author(s):  
PATRICK GARNERO ◽  
NADINE CHARNI-BEN TABASSI ◽  
NATHALIE VOORZANGER-ROUSSELOT
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
C Reactive Protein ◽  
Radiological Progression ◽  
Reactive Protein ◽  
Important Mediator ◽  
Risk Of Progression ◽  
Radiological Damage ◽  
Dickkopf 1

ObjectiveDickkopf-1 (Dkk-1) regulates bone remodeling in animal models of inflammatory arthritis, but its role in patients with rheumatoid arthritis (RA) remains unclear.MethodsBaseline circulating Dkk-1 was measured in 113 patients with RA (< 3 yrs) who received etanercept (10 or 25 mg twice/week, n = 63) or methotrexate alone (n = 40) for 1 year. Progression was assessed by changes in radiological Sharp score.ResultsIncreased Dkk-1 was associated with a higher risk of progression of bone erosion, independently of age, sex, baseline radiological damage, C-reactive protein, and disease activity in patients treated with etanercept.ConclusionDkk-1 may be an important mediator of bone erosion in patients with RA.

scholarly journals Delivery of miR-146a to Ly6Chigh Monocytes Inhibits Pathogenic Bone Erosion in Inflammatory Arthritis

Theranostics ◽  
2018 ◽  
Vol 8 (21) ◽  
pp. 5972-5985 ◽  
Author(s):  
Meryem Ammari ◽  
Jessy Presumey ◽  
Clara Ponsolles ◽  
Gautier Roussignol ◽  
Christine Roubert ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion

scholarly journals Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fiona K. Jones ◽  
Andrei Stefan ◽  
Alasdair G. Kay ◽  
Mairead Hyland ◽  
Rebecca Morgan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Cell Signalling ◽  
Collagen Type I ◽  
Type I ◽  
Wild Type ◽  
Differentiation Potential

AbstractRheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSC biology. MSCs isolated from bone marrow of wild type and Sdc3−/− mice were used to assess immunophenotype, differentiation, adhesion and migration properties and cell signalling pathways. While both cell types show similar differentiation potential and forward scatter values, the cell complexity in wild type MSCs was significantly higher than in Sdc3−/− cells and was accompanied by lower spread surface area. Moreover, Sdc3−/− MSCs adhered more rapidly to collagen type I and showed a dramatic increase in AKT phosphorylation, accompanied by a decrease in ERK1/2 phosphorylation compared with control cells. In a mouse model of antigen-induced inflammatory arthritis, intraarticular injection of Sdc3−/− MSCs yielded enhanced efficacy compared to injection of wild type MSCs. In conclusion, our data suggest that syndecan-3 regulates MSC adhesion and efficacy in inflammatory arthritis, likely via induction of the AKT pathway.

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