TLRs Play Crucial Roles in Regulating RA Synoviocyte

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease comparing the inflammation of synovium. Macrophage-like synoviocytes and fibroblast-like synoviocytes (synoviocytes) are crucial ingredients of synovium. Therein, a lot of research has focused on synoviocytes. Researches demonstrated that TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 TLR7 and TLR9 are expressed in synoviocyte. Additionally, the expression of TLR2, TLR3, TLR4 and TLR5 is increased in RA synoviocyte. In this paper, we review the exact role of TLR2, TLR3, TLR4 and TLR5 participate in regulating the production of inflammatory factors in RA synoviocyte. Furthermore, we discuss the role of vasoactive intestinal peptide (VIP), MicroRNA, Monome of Chinese herb and other cells (Monocyte and T cell) influence the function of synoviocyte by regulating TLRs. The activation of toll-like receptors (TLRs) in synoviocyte leads to the aggravation of arthritis, comparing with angiogenesis and bone destruction. Above all, TLRs are promising targets for managing RA.

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Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.673263 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingpan Lin ◽

Lu Gao ◽

Yanke Lin ◽

Shuai Wang ◽

Zemin Yang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Destruction ◽

Systemic Exposure ◽

Inflammatory Factors ◽

Systemic Autoimmune Disease ◽

Active Ingredients ◽

Tnf Α ◽

Exposure Levels ◽

Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

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Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Mediators of Inflammation ◽

10.1155/2020/8295149 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Xiao-Bo Luo ◽

Jian-Cheng Xi ◽

Zhen Liu ◽

Yu Long ◽

Li-tao Li ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor Receptor ◽

Dependent Manner ◽

Autoimmune Inflammatory Disease ◽

Specific Protease ◽

Inflammatory Processes ◽

Ubiquitin Specific Protease ◽

Signaling Activation ◽

Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

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Nanomedicine: an emerging era of theranostics and therapeutics for rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/kez286 ◽

2019 ◽

Vol 58 (10) ◽

pp. 1715-1721 ◽

Cited By ~ 3

Author(s):

Naila Qamar ◽

Ammara Arif ◽

Attya Bhatti ◽

Peter John

Keyword(s):

Rheumatoid Arthritis ◽

Targeted Therapy ◽

Side Effects ◽

Inflammatory Disease ◽

Therapeutic Strategy ◽

Bone Destruction ◽

Mortality Rates ◽

Autoimmune Inflammatory Disease ◽

Target Side ◽

Novel Therapeutic

Abstract RA is a multifactorial autoimmune inflammatory disease characterized by synovitis, bone destruction and joint dysfunction that leads to shortening of lifespan and increased mortality rates. Currently available treatments of RA, by controlling various symptoms, only delay disease progression and have their own side effects. Consequently, there is the need for a novel therapeutic strategy that offers a more sustainable and biocompatible solution. Nanomedicine is a modern branch of nanobiotechnology that provides targeted therapy to inflamed rheumatic joints and thus prevents unwanted off-target side effects. This review highlights various nanotheranostic and nanotherapeutic strategies that are currently being used for the treatment of RA.

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The Role of miR-382-5p in Rheumatoid Arthritis: An In Vitro Study with Fibroblast-Like Synoviocytes

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2227 ◽

2020 ◽

Vol 10 (2) ◽

pp. 169-175

Author(s):

Deqian Meng ◽

Wenyou Pan ◽

Ju Li

Keyword(s):

Rheumatoid Arthritis ◽

In Vitro Study ◽

Underlying Mechanism ◽

High Morbidity ◽

Systemic Autoimmunity ◽

Autoimmune Inflammatory Disease ◽

Proliferation And Invasion ◽

Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease with high morbidity. MiR-382-5p may be associated with progression from systemic autoimmunity to RA inflammation. The present study aims to investigate the underlying mechanism of miR-382-5p in the pathogenesis of RA. In present study, the decreased expression of miR-382-5p was observed in RA-FLSs. Furthermore, miR-382-5p overexpression inhibited the proliferation and invasion of RA-FLS cells. In addition, miR-382-5p overexpression inhibited the release of inflammatory cytokines and promoted apoptosis of RA-FLS cells. Finally, miR-382-5p overexpression induced inactivation of TLR4/NF-κB/Cox2 signaling pathway. Our findings implied that miR-382-5p exerts regulative effect on pathogenesis of RA and indicated that miR-382-5p may represent as an effective therapeutic target in the clinical treatment of RA.

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Moxibustion of Zusanli (ST36) and Shenshu (BL23) Alleviates Cartilage Degradation through RANKL/OPG Signaling in a Rabbit Model of Rheumatoid Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6436420 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yang Chen ◽

Haijun Li ◽

Xiaochao Luo ◽

Huahui Liu ◽

Yumei Zhong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Responses ◽

Musculoskeletal Diseases ◽

Alternative Therapy ◽

Rabbit Model ◽

Bone Destruction ◽

Cartilage Degradation ◽

Protective Effects ◽

Rankl Mrna ◽

Autoimmune Inflammatory Disease

Rheumatoid arthritis (RA) is a systemic and chronic autoimmune inflammatory disease characterized by severe synovial hyperplasia associated with progressive cartilage degradation. Due to the severe pain and disability caused by RA, effective therapeutic strategies that could simultaneously alleviate the inflammatory response and delay the disease progression are urgently needed. As a major alternative therapy in traditional Chinese medicine, moxibustion has been demonstrated that it could reduce the chronic inflammatory responses of a series of musculoskeletal diseases; however, whether moxibustion has protective effects on RA is still unclear. To investigate the effects of moxibustion on RA, moxibustion was applied to Zusanli (ST36) and Shenshu (BL23) acupoints in a RA rabbit model. HE staining of articular cartilage showed that moxibustion alleviated the cartilage degradation and bone destruction. In addition, moxibustion decreased the osteoclast number in RA rabbits. Real-time PCR revealed that moxibustion decreased the expression of RANKL mRNA while increased the expression of OPG mRNA, indicating a restoration of the balance between osteogenesis and osteoclastogenesis. Taken together, our results indicated that moxibustion had promising antiarthritic effects and could be an useful alternative method in RA therapeutics.

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The role of YY1 in the pathogenesis of rheumatoid arthritis: A tale of cytokines, ncRNAs, and aberrant fibroblast-like synoviocytes (FLSs)

YY1 in the Control of the Pathogenesis and Drug Resistance of Cancer ◽

10.1016/b978-0-12-821909-6.00018-3 ◽

2021 ◽

pp. 311-335

Author(s):

Yuhao Wang ◽

Benjamin Bonavida

Keyword(s):

Rheumatoid Arthritis ◽

Fibroblast Like Synoviocytes

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Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes

Microscopy and Microanalysis ◽

10.1017/s1431927617012399 ◽

2017 ◽

Vol 23 (5) ◽

pp. 1002-1012 ◽

Cited By ~ 4

Author(s):

Zhanhui Su ◽

Han Sun ◽

Man Ao ◽

Chunying Zhao

Keyword(s):

Rheumatoid Arthritis ◽

Atomic Force Microscopy ◽

Inflammatory Responses ◽

Bone Destruction ◽

Microscopy Study ◽

Primary Role ◽

Force Microscopy ◽

Atomic Force ◽

Anti Inflammatory ◽

Fibroblast Like Synoviocytes

AbstractHigh-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.

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The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification

Inflammation ◽

10.1007/s10753-020-01357-z ◽

2020 ◽

Cited By ~ 1

Author(s):

Chenyang Yu ◽

Caihua Zhang ◽

Zhihui Kuang ◽

Qiang Zheng

Keyword(s):

Vascular Calcification ◽

Nlrp3 Inflammasome ◽

Periodontal Diseases ◽

Bone Destruction ◽

Bone Diseases ◽

Sterile Inflammation ◽

Inflammatory Factors ◽

Bone Homeostasis ◽

Caspase 1

Abstract Continuous stimulation of inflammation is harmful to tissues of an organism. Inflammatory mediators not only have an effect on metabolic and inflammatory bone diseases but also have an adverse effect on certain genetic and periodontal diseases associated with bone destruction. Inflammatory factors promote vascular calcification in various diseases. Vascular calcification is a pathological process similar to bone development, and vascular diseases play an important role in the loss of bone homeostasis. The NLRP3 inflammasome is an essential component of the natural immune system. It can recognize pathogen-related molecular patterns or host-derived dangerous signaling molecules, recruit, and activate the pro-inflammatory protease caspase-1. Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce corresponding mature cytokines or recognizes and cleaves GSDMD to mediate cell pyroptosis. In this review, we discuss the role of NLRP3 inflammasome in bone diseases and vascular calcification caused by sterile or non-sterile inflammation and explore potential treatments to prevent bone loss.

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