scholarly journals Non-classical monocytes as mediators of tissue destruction in arthritis

2018 ◽  
Vol 77 (10) ◽  
pp. 1490-1497 ◽  
Author(s):  
Antonia Puchner ◽  
Victoria Saferding ◽  
Michael Bonelli ◽  
Yohei Mikami ◽  
Melanie Hofmann ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Destruction ◽  
Joint Damage ◽  
Bone Destruction ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Monocyte Subsets ◽  
Tissue Destruction ◽  
Local Bone ◽  
Classical Monocytes

ObjectivesBone destruction in rheumatoid arthritis is mediated by osteoclasts (OC), which are derived from precursor cells of the myeloid lineage. The role of the two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2) and non-classical monocytes (which are CD115 positive, but low in Ly6C and CCR2), in serving as precursors for OC in arthritis is still elusive.MethodsWe investigated CCR2−/− mice, which lack circulating classical monocytes, crossed into hTNFtg mice for the extent of joint damage. We analysed monocyte subsets in hTNFtg and K/BxN serum transfer arthritis by flow cytometry. We sorted monocyte subsets and analysed their potential to differentiate into OC and their transcriptional response in response to RANKL by RNA sequencing. With these data, we performed a gene ontology enrichment analysis and gene set enrichment analysis.ResultsWe show that in hTNFtg arthritis local bone erosion and OC generation are even enhanced in the absence of CCR2. We further show the numbers of non-classical monocytes in blood are elevated and are significantly correlated with histological signs of joint destruction. Sorted non-classical monocytes display an increased capacity to differentiate into OCs. This is associated with an increased expression of signal transduction components of RANK, most importantly TRAF6, leading to an increased responsiveness to RANKL.ConclusionTherefore, non-classical monocytes are pivotal cells in arthritis tissue damage and a possible target for therapeutically intervention for the prevention of inflammatory joint damage.

scholarly journals Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis

2020 ◽  
Vol 21 (11) ◽  
pp. 4145 ◽  
Author(s):  
Takahiko Akagi ◽  
Tomoyuki Mukai ◽  
Takafumi Mito ◽  
Kyoko Kawahara ◽  
Shoko Tsuji ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Tumor Necrosis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Ang Ii ◽  
Necrosis Factor ◽  
Systemic Bone Loss

Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.

scholarly journals The Death Receptor 3–TNF-like protein 1A pathway drives adverse bone pathology in inflammatory arthritis

2008 ◽  
Vol 205 (11) ◽  
pp. 2457-2464 ◽  
Author(s):  
Melanie Jane Bull ◽  
Anwen Siân Williams ◽  
Zarabeth Mecklenburgh ◽  
Claudia Jane Calder ◽  
Jason Peter Twohig ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Destruction ◽  
Death Receptor ◽  
Bone Destruction ◽  
Chronic Inflammatory Disease ◽  
Joint Disease ◽  
Bone Pathology ◽  
Novel Target ◽  
Death Receptor 3

Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints that is associated with cartilage and bone destruction. Death Receptor 3 (DR3), a tumor necrosis factor (TNF) receptor superfamily member, has recently been associated with the pathogenesis of RA. We demonstrate that absence of DR3 confers resistance to the development of adverse bone pathology in experimental antigen-induced arthritis (AIA). DR3ko mice exhibited a reduction in all histopathological hallmarks of AIA but, in particular, failed to develop subchondral bone erosions and were completely protected from this characteristic of AIA. In contrast, TNF-like protein 1A (TL1A), the ligand for DR3, exacerbated disease in a dose- and DR3-dependent fashion. Analysis of osteoclast number within AIA joint revealed a reduction in areas susceptible to bone erosion in DR3ko mice, whereas in vitro osteoclastogenesis assays showed that TL1A could directly promote osteoclastogenesis in mouse and man. Treatment with antagonistic anti-TL1A mAb protected animals in a systemic model of RA disease collagen-induced arthritis. We therefore conclude that the DR3–TL1A pathway regulates joint destruction in two murine models of arthritis and represents a potential novel target for therapeutic intervention in inflammatory joint disease.

scholarly journals S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Irene Di Ceglie ◽  
Peter L. E. M. van Lent ◽  
Edwin J. W. Geven ◽  
Marije I. Koenders ◽  
Arjen B. Blom ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Receptor Antagonist ◽  
Bone Marrow Cells ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Joint Inflammation ◽  
Cartilage Degeneration ◽  
Old Mice

Abstract Background Excessive osteoclast activity, which is strongly stimulated by pro-inflammatory mediators, results in bone and cartilage degeneration as central features of many arthritides. Levels of the alarmin S100A8/A9 and interleukin (IL)-1β are both increased in arthritis patients and correlate with disease activity and progression of tissue erosion. We previously presented S100A8/A9 as a good biomarker for joint inflammation and arthritis pathology under circumstances of high IL-1 signaling in mice that lack the gene encoding IL-1 receptor antagonist (Il1rn−/− mice). Here, we investigated whether S100A8/A9 is also actively involved in the development of joint inflammation and both cartilage and bone pathology under these conditions by comparing Il1rn−/− mice with mice that have an additional deficiency for S100a9 (Il1rn−/−XS100a9−/−). Methods Il1rn−/−XS100a9−/− on a BALB/c background were obtained by crossing S100a9−/− mice and Il1rn−/− mice. Arthritis incidence and severity were macroscopically scored. Myeloid cell populations in the bone marrow and spleen were determined using flow cytometry. In vitro osteoclastogenesis of bone marrow cells was evaluated with TRAP staining. Microscopic joint inflammation, cartilage degeneration, and bone destruction were evaluated using histology of ankle joints of 12- and 20-week-old mice. Results Macroscopically scored arthritis severity was comparable between Il1rn−/− and Il1rn−/−XS100a9−/− mice. Inflammation, cartilage erosion, and bone erosion were clearly present in 12-week-old mice of both strains lacking Il1rn−/−, but not significantly different between Il1rn−/−XS100a9−/− and Il1rn−/−. Moreover, we observed that the numbers of neutrophils and monocytes were increased by the absence of Il1rn, which was affected by the absence of S100a9 only in the spleen but not in the bone marrow. In line with our other findings, the absence of S100a9 did not affect the osteoclastogenic potential of osteoclast precursors in the absence of Il1rn. Finally, in agreement with the findings in early arthritis development in 12-week-old mice, cartilage and bone erosion in 20-week-old mice was significantly higher in both Il1rn−/− strains, but the additional absence of S100a9 did not further affect tissue pathology. Conclusion S100A8/A9 deficiency does not significantly affect inflammation and joint destruction in mice with high IL1β signaling suggesting that S100A8/A9 is not essential for the development of arthritis under these conditions.

scholarly journals Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Jiah Yeom ◽  
Dong Joon Yim ◽  
Seongho Ma ◽  
Young-Hee Lim
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Bone Destruction ◽  
In Vivo Studies ◽  
Propionibacterium Freudenreichii ◽  
Limited Information ◽  
Collagen Induced Arthritis

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

scholarly journals Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis

2019 ◽  
Vol 6 (1) ◽  
pp. e000331 ◽  
Author(s):  
Ze-Min Lin ◽  
Yu-Ting Liu ◽  
Yan-Sheng Xu ◽  
Xiao-Qian Yang ◽  
Feng-Hua Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Experimental Arthritis ◽  
Raw264.7 Cells ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Therapeutic Benefits

ObjectiveRheumatoid arthritis is an autoimmune disease characterised by inflammation and bone loss, leading to joint destruction and deformity. The cervus and cucumis polypeptide (CCP) injection, one of the traditional Chinese medicine injections combined extracts from deer horn and sweet melon seeds, is widely used to treat arthritis and bone fracture in China. The present study investigated the therapeutic efficacy and mechanism of CCP on pathological immune cells and bone homoeostasis in rodent experimental arthritis.MethodsThe effects of CCP (4 mg/kg and 2 mg/kg) on clinical arthritis symptoms, bone erosion, proinflammatory cytokines and pathological immune cells induced by complete Freund’s adjuvant was evaluated in male Sprague-Dawley rats. The impacts of CCP (2 mg/kg) on joint erythema and swelling, production of pathogenic antibodies and the proportion of inflammatory cells were assessed in collagen-induced arthritis (CIA) in DBA/1J mice. Regulation of osteoclastogenesis by CCP was observed in the murine macrophage-like RAW264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).ResultsCCP administration significantly prevented disease progression in both adjuvant-induced arthritis (AIA) rats and CIA mice. The therapeutic benefits were accompanied by reduction of paw oedema, reversed bone destruction, decreased pathological changes and osteoclast numbers in joints in AIA rats, as well as attenuated clinical manifestation and autoantibodies production in CIA mice. Meanwhile, in vitro supplemented of CCP concentration dependently inhibited RANKL/M-CSF-induced osteoclast differentiation, without showing cytotoxicity in RAW264.7 cells. Further, the presence of CCP dampened the augmented downstream signalling transduction as well as activation of osteoclast-specific genes and transcription factors induced by RANKL/M-CSF in RAW264.7 cells.ConclusionOur study suggested that the therapeutic effects of CCP in experimental arthritis could be attributed to its intervention on RANKL-induced osteoclastogenesis signalling pathway in osteoclast precursor cells.

scholarly journals Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis

Rheumatology ◽  
2020 ◽  
Author(s):  
Shixian Chen ◽  
Chunqing Guo ◽  
Ran Wang ◽  
Zhitao Feng ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Mouse Models ◽  
Th17 Cells ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Suppressor Cells ◽  
Th 17 ◽  
Autoimmune Conditions

Abstract Objectives While myeloid-derived suppressor cells (MDSCs) were previously shown to promote a proinflammatory T helper (Th) 17 response in autoimmune conditions, a potential impact of the MDSC-Th17 immune axis on abnormal bone destruction in RA remains largely unknown. Methods We investigated the correlation between the frequency of MDSCs or its subsets and joint destruction in RA patients. The reciprocal actions of patient-derived MDSCs and Th17 cells were studied using osteoclast (OC) differentiation and bone resorption assays in vitro, which were further validated using mouse models of RA. Contribution of MDSCs to osteoclastogenesis and bone erosion in vivo was determined by depletion or transfer of MDSCs. Results Human MDSCs, particularly monocytic MDSCs (M-MDSCs), exhibit inherent OC-differentiating capacity and positively correlate with clinical bone erosion in RA patients. Strikingly, patient-derived M-MDSCs can program Th17 cells towards a pro-osteoclastogenic phenotype, which in return potentiates OC differentiation via the receptor activator of nuclear factor κΒ ligand (RANK-L)-RANK signalling. This enhanced osteolysis driven by the reciprocal actions of M-MDSCs and Th17 cells is further confirmed using mouse models of RA. Selective depletion of M-MDSCs significantly ameliorates osteoclastogenesis and disease severity in arthritic mice, whereas transfer of M-MDSCs aggravates bone erosion associated with increased OCs in recipient mice. Conclusion Our findings highlight the functional plasticity of MDSCs and identify a novel pro-osteoclastogenic pathway governed by interplay between myeloid cells and T lymphocytes in autoimmune RA.

Deficiency of sorting nexin 10 prevents bone erosion in collagen-induced mouse arthritis through promoting NFATc1 degradation

2015 ◽  
Vol 75 (6) ◽  
pp. 1211-1218 ◽  
Author(s):  
Chun Zhou ◽  
Yan You ◽  
Weixing Shen ◽  
Yi-Zhun Zhu ◽  
Jing Peng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Osteoclast Differentiation ◽  
Critical Index ◽  
Bone Destruction ◽  
Wild Type ◽  
Clinical Role ◽  
Sorting Nexin

ObjectivePeriarticular and subchondral bone erosion in rheumatoid arthritis caused by osteoclast differentiation and activation is a critical index for diagnosis, therapy and monitoring of the disease. Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation of endosomal sorting, has been implicated to play an important clinical role in malignant osteopetrosis. Here we studied the roles and precise mechanisms of SNX10 in the bone destruction of collagen-induced arthritis (CIA) mice.MethodsThe role of SNX10 in bone destruction was evaluated by a CIA mice model which was induced in male SNX10−/− mice and wild type littermates. The mechanism was explored in osteoclasts induced by receptor activator of nuclear factor κB ligand from bone marrow mononuclear cells of wild type and SNX10−/− mice.ResultsSNX10 knockout prevented bone loss and joint destruction in CIA mice with reduced serum levels of TNF-α, interleukin 1β and anticollagen IgG 2α antibody. SNX10 deficiency did not block osteoclastogenesis, but significantly impaired osteoclast maturation and bone-resorption function by disturbing the formation of actin belt. The production of TRAP, CtsK and MMP9 in SNX10−/− osteoclasts was significantly inhibited, and partially restored by SNX10 overexpression. We further demonstrated that the degradation of NFATc1 was accelerated in SNX10−/− osteoclasts causing an inhibition of integrin β3-Src-PYK2 signalling.ConclusionsOur study discloses a crucial role and novel mechanism for SNX10 in osteoclast function, and provides evidence for SNX10 as a promising novel therapeutic target for suppression of immune inflammation and bone erosion in rheumatoid arthritis.

scholarly journals High-resolution ultrasound evaluation in the follow-up of treat to target urate-lowering therapy in gout: an observational study

2020 ◽  
Author(s):  
Weijing Zhang ◽  
Di Zhao ◽  
Min Wu ◽  
Zhibin Jin ◽  
Huayong Zhang
Keyword(s):  
Bone Erosion ◽  
Joint Damage ◽  
Bone Destruction ◽  
Treat To Target ◽  
Short Axis ◽  
Crystal Deposition ◽  
Lowering Therapy ◽  
Ultrasound Evaluation ◽  
Significant Difference

Abstract Background: The monitoring of treat-to-target (T2T) urate-lowering therapy (ULT) for gout is crucial for the assessing treatment response. However, evidence is lacking about clinical remission on ultrasound (US). The aim of this study was to observe the changes in three outcome domains (urate deposition, joint inflammation and bone erosion) in patients with ULT within 1 year, evaluate the effect of target treatment and analyse the relationships between clinical factors and US features. Methods: The elementary lesions of the bilateral knee, ankle and first metatarsophalangeal joints were evaluated by US before and after 3,6 and 12months of treatment. Urate deposition was assessed by the maximum long and short axis diameters of the tophi and dichotomous data of the double-contour (DC) sign and aggregates. After each follow-up, the most obvious lesions were selected for repeated observation. The effective clearance rates of these three signs in different time groups were compared. A Global OMERACT–EULAR Synovitis Score (GLOESS) was calculated for these three paired joints to observe the remission and recurrence of inflammation. Bone destruction was scored at each time point. The correlation between serum uric acid (sUA) levels and tophi size changes was analysed. Results: This cohort contained 79 patients. The long and short axis diameters of tophi showed a different descending tendency. The decrease of sUA levels correlated with the decrease of long axis values, but not with the short. For tophi, there was no significant difference in the clearance rate between different time groups, while for DC sign and aggregates, significant differences were found by paired comparison. The GLOESS was significantly lower after 6 months of therapy. Bone erosion had not been improved after 1 year of ULT.Conclusion: The decrease in sUA levels was not completely parallel to the decrease in tophi size. ULT with different intensities should be formulated according to different crystal deposition conditions under US assessment. Subclinical inflammation was gradually controlled after 6 months of therapy and can be sensitively observed by US. Joint damage was relatively stable within 12 months of ULT.

scholarly journals Secretory Leukocyte Protease Inhibitor Suppresses the Inflammation and Joint Damage of Bacterial Cell Wall–Induced Arthritis

1999 ◽  
Vol 190 (4) ◽  
pp. 535-542 ◽  
Author(s):  
Xiao-yu Song ◽  
Li Zeng ◽  
Wenwen Jin ◽  
John Thompson ◽  
Diane E. Mizel ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protease Inhibitor ◽  
Therapeutic Potential ◽  
Joint Damage ◽  
Bone Destruction ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Systemic Delivery ◽  
Tissue Destruction ◽  
Streptococcal Cell Wall ◽  
And Cartilage

Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor α and nuclear factor κB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases.

Osteosarcoma of the jaws: a literature review

2020 ◽  
Vol 16 ◽  
Author(s):  
Francesco Ricotta ◽  
Massimo Bassi ◽  
Nicola Tomasetti ◽  
Angelo Campobassi ◽  
Vincenzo Maiolo ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
State Of The Art ◽  
Bone Erosion ◽  
Tumor Resection ◽  
Bone Destruction ◽  
Cell Type ◽  
Complete Tumor Resection ◽  
Predominant Cell Type ◽  
Bone Changes ◽  
Complete Tumor

: Osteosarcoma of the jaws (OSJ) is a relatively rare disease, accounting for between 2% and 10% of all cases of osteosarcoma, it is morphologically and radiologically identical to the trunk and extremity variant, but distinct in several crucial aspects. : The lesion is characterized by sarcomatous cells which produces a variable amount of osteoid bone. It arises centrally within the bone and can be subdivided into osteoblastic, chondroblastic and fibroblastic subtype, depending on the predominant cell type. : Radiographically, these tumors display a spectrum of bone changes from well-demarcated borders to lytic bone destruction with indefinite margins and variable cortical bone erosion or, in some cases, images of sclerotic bone. Therapeutic options for OSJ include surgery, chemotherapy and radiotherapy, which are employed according to age of the patient, histological classification and localization of the tumor. Today there is no a general consensus in the treatment guidelines for the OSJ though surgery represents the key of the treatment. The main prognostic factor deeply influencing the patient's prognosis remains the complete tumor resection with negative surgical margins. : The aim of the present review is to describe the state of the art regarding diagnostic and surgical treatment aspects of the primary osteosarcoma of the jaws.

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