Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis

In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferonγ[IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.

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Absence of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling protects against collagen-induced arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-203371 ◽

2013 ◽

Vol 74 (1) ◽

pp. 211-219 ◽

Cited By ~ 9

Author(s):

M I P Ramos ◽

O N Karpus ◽

P Broekstra ◽

S Aarrass ◽

S E Jacobsen ◽

...

Keyword(s):

Tyrosine Kinase ◽

Acute Phase ◽

Ex Vivo ◽

Late Phase ◽

Joint Destruction ◽

Chronic Phase ◽

Foxp3 Expression ◽

Cartilage Destruction ◽

Collagen Induced Arthritis ◽

Clinical Arthritis

ObjectiveComprehending the mechanisms that regulate activation of autoreactive T cells and B cell antibody production is fundamental for understanding the breakdown in self-tolerance and development of autoimmunity. Here we studied the role of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling in the pathogenesis of collagen-induced arthritis (CIA).MethodsCIA was induced in mice lacking Flt3L (Flt3L−/−)and wild-type (WT) littermates (C57/BL6, 8–10 weeks old). Mice were killed in the initial phase (acute phase: experiment 1) and late phase (chronic phase: experiment 2) of the disease. Arthritis severity was assessed using a semiquantitative scoring system (0–4), and histological analysis of cellular infiltration, cartilage destruction and peptidoglycan loss was performed. Phenotypic and functional analysis of T and B cells, FoxP3 expression, activation and lymphocyte costimulatory markers, and cytokine production were performed ex vivo by flow cytometry in lymph nodes. Serum collagen type II (CII)-specific antibodies were measured by ELISA.ResultsFlt3L−/−mice showed a marked decrease in clinical arthritis scores and incidence of arthritis in both acute and chronic phases of CIA compared with WT mice. Moreover, decreased synovial inflammation and joint destruction was observed. Both the magnitude and quality of T cell responses were altered in Flt3L−/−. In the acute phase, the amount of CII-specific IgG2a antibodies was lower in Flt3L−/−than WT mice.ConclusionsThese results strongly suggest a role for Flt3L signalling in the development of arthritis.

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Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice

Biochemical Pharmacology ◽

10.1016/j.bcp.2006.08.027 ◽

2007 ◽

Vol 73 (1) ◽

pp. 136-146 ◽

Cited By ~ 76

Author(s):

Na Lin ◽

Chunfang Liu ◽

Cheng Xiao ◽

Hongwei Jia ◽

Keisuke Imada ◽

...

Keyword(s):

Cartilage Destruction ◽

Collagen Induced Arthritis ◽

And Cartilage

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Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Arthritis & Rheumatism ◽

10.1002/art.20001 ◽

2004 ◽

Vol 50 (2) ◽

pp. 650-659 ◽

Cited By ~ 512

Author(s):

Erik Lubberts ◽

Marije I. Koenders ◽

Birgitte Oppers-Walgreen ◽

Liduine van den Bersselaar ◽

Christina J. J. Coenen-de Roo ◽

...

Keyword(s):

Bone Erosion ◽

Joint Inflammation ◽

Cartilage Destruction ◽

Interleukin 17 ◽

Collagen Induced Arthritis

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Chondrocyte Targeting Gold Nanoparticles Protect Growth Plate Against Inflammatory Damage By Maintaining Cartilage Balance

10.21203/rs.3.rs-1078970/v1 ◽

2021 ◽

Author(s):

Xue Bai ◽

Hongyan Sun ◽

Lina Jia ◽

Junjie Xu ◽

Peng Zhang ◽

...

Keyword(s):

Gold Nanoparticles ◽

Growth Plate ◽

Inflammatory Cytokines ◽

Degradation Rate ◽

Cartilage Destruction ◽

Chondrocyte Apoptosis ◽

Inflammatory Damage ◽

Clinical Challenge ◽

Ecm Degradation ◽

Induced Apoptosis

Abstract Background: Cartilage destruction caused by inflammation is a clinical challenge. Many studies have investigated cartilage destruction in adults, but little research was conducted on children. Results: The gaps without chondrocytes and ECM between the proliferative and hypertrophy zones of the GP cartilage were formation after the treatment of LPS, but the gaps were not observed in the AuNPs + LPS group. This finding can be attributed to the capability of AuNPs to target to the chondrocytes and reduce the release of inflammatory cytokines and secretion of ECM degradation factors induced by LPS. And then, the LPS-induced apoptosis rate of mouse chondrocytes and ECM degradation rate were inhibited. Finally, the balance of catabolic and anabolic factors in the ECM was maintained.Conclusion: These findings indicate that AuNPs can partially protect the cartilage of children from inflammatory damage by suppressing chondrocyte apoptosis and ECM degradation.

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Galectin 3 Deficiency Alters Chondrocyte Primary Cilium Formation and Exacerbates Cartilage Destruction via Mitochondrial Apoptosis

International Journal of Molecular Sciences ◽

10.3390/ijms21041486 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1486 ◽

Cited By ~ 2

Author(s):

Narjès Hafsia ◽

Marine Forien ◽

Félix Renaudin ◽

Delphine Delacour ◽

Pascal Reboul ◽

...

Keyword(s):

Primary Cilium ◽

Primary Cilia ◽

Mitochondrial Pathway ◽

Cartilage Destruction ◽

Terminal Deoxynucleotidyl Transferase ◽

Chondrocyte Apoptosis ◽

Cytochrome C Release ◽

Cilium Formation ◽

Galectin 3

Mechanical overload and aging are the main risk factors of osteoarthritis (OA). Galectin 3 (GAL3) is important in the formation of primary cilia, organelles that are able to sense mechanical stress. The objectives were to evaluate the role of GAL3 in chondrocyte primary cilium formation and in OA in mice. Chondrocyte primary cilium was detected in vitro by confocal microscopy. OA was induced by aging and partial meniscectomy of wild-type (WT) and Gal3-null 129SvEV mice (Gal3−/−). Primary chondrocytes were isolated from joints of new-born mice. Chondrocyte apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cytochrome c release. Gene expression was assessed by qRT-PCR. GAL3 was localized at the basal body of the chondrocyte primary cilium. Primary cilia of Gal3−/− chondrocytes were frequently abnormal and misshapen. Deletion of Gal3 triggered premature OA during aging and exacerbated joint instability-induced OA. In both aging and surgery-induced OA cartilage, levels of chondrocyte catabolism and hypertrophy markers and apoptosis were more severe in Gal3−/− than WT samples. In vitro, Gal3 knockout favored chondrocyte apoptosis via the mitochondrial pathway. GAL3 is a key regulator of cartilage homeostasis and chondrocyte primary cilium formation in mice. Gal3 deletion promotes OA development.

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Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction

Arthritis & Rheumatism ◽

10.1002/1529-0131(199801)41:1<110::aid-art14>3.0.co;2-g ◽

1998 ◽

Vol 41 (1) ◽

pp. 110-121 ◽

Cited By ~ 132

Author(s):

J. S. Mudgett ◽

N. I. Hutchinson ◽

N. A. Chartrain ◽

A. J. Forsyth ◽

J. McDonnell ◽

...

Keyword(s):

Cartilage Destruction ◽

Collagen Induced Arthritis ◽

Deficient Mice ◽

And Cartilage

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DMY protects the knee joints of rats with collagen-induced arthritis by inhibition of NF-κB signaling and osteoclastic bone resorption

Food & Function ◽

10.1039/d0fo00396d ◽

2020 ◽

Vol 11 (7) ◽

pp. 6251-6264

Author(s):

Jing Wu ◽

Kai-Jian Fan ◽

Qi-Shan Wang ◽

Bing-Xin Xu ◽

Qing Cai ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Animal Model ◽

Articular Cartilage ◽

Bone Resorption ◽

Bone Erosion ◽

Cartilage Destruction ◽

Osteoclastic Bone Resorption ◽

Knee Joints ◽

Collagen Induced Arthritis

Collagen-induced arthritis (CIA) is a widely used animal model for studying rheumatoid arthritis (RA), which manifests serious joint dysfunction, progressive bone erosion and articular cartilage destruction.

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Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208406 ◽

2016 ◽

Vol 75 (11) ◽

pp. 2045-2052 ◽

Cited By ~ 22

Author(s):

Yoonkyung Won ◽

Youngnim Shin ◽

Churl-Hong Chun ◽

Yongsik Cho ◽

Chul-Won Ha ◽

...

Keyword(s):

Molecular Mechanisms ◽

Expression Profiles ◽

Hypoxia Inducible Factor ◽

Gene Expression Profiles ◽

Cartilage Destruction ◽

Terminal Deoxynucleotidyl Transferase ◽

Chondrocyte Apoptosis ◽

Double Knockout ◽

Nicotinamide Phosphoribosyltransferase ◽

Human And Mouse

ObjectiveThe zinc-ZIP8-MTF1 axis induces metallothionein (MT) expression and is a catabolic regulator of experimental osteoarthritis (OA) in mice. The main aim of the current study was to explore the roles and underlying molecular mechanisms of MTs in OA pathogenesis.MethodsExperimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of adenovirus carrying a target gene (Ad-Zip8, Ad-Mtf1, Ad-Epas1, Ad-Nampt, Ad-Mt1 or Ad-Mt2) into wild type, Zip8fl/fl; Col2a1-Cre, Mtf1fl/fl; Col2a1-Cre and Mt1/Mt2 double knockout mice. Primary cultured mouse chondrocytes were infected with Ad-Mt1 or Ad-Mt2, and gene expression profiles analysed via microarray and reverse transcription-PCR. Proteins in human and mouse OA cartilage were identified via immunostaining. Chondrocyte apoptosis in OA cartilage was determined using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL).ResultsMTs were highly expressed in human and mouse OA cartilage. Hypoxia-inducible factor 2α, nicotinamide phosphoribosyltransferase and several proinflammatory cytokine pathways, as well as the zinc-ZIP8-MTF1 axis were identified as upstream regulators of MT expression. Genetic deletion of Mt1 and Mt2 enhanced cartilage destruction through increasing chondrocyte apoptosis. Unexpectedly, aberrant overexpression of MT2, but not MT1, induced upregulation of matrix-degrading enzymes and downregulation of matrix molecules through nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activation, ultimately leading to OA.ConclusionsMTs play an antiapoptotic role in post-traumatic OA. However, aberrant and chronic upregulation of MT2 triggers an imbalance between chondrocyte anabolism and catabolism, consequently accelerating OA development. Our findings collectively highlight pleiotropic roles of MTs as regulators of chondrocyte apoptosis as well as catabolic and anabolic pathways during OA pathogenesis.

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