Cell Animal Models Research Articles

Regeneration of mandibular condyle cartilage damage by transplantation of mesenchymal stromal cells in animal model

Background: Repair of cartilage damage in mandibular condyles is one of the main challenges in temporomandibular joint pathology. Cellular therapy based on mesenchymal stromal cells (MSCs) transplantation has been postulated for inducing cartilage regeneration.

Tubulin is actively exported from the nucleus through the Exportin1/CRM1 pathway

Microtubules of all eukaryotic cells are formed by α- and β-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and β-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase.

MP06-08 THE METABOLIC HORMONE LEPTIN PROMOTES PROSTATE SMOOTH MUSCLE CONTRACTION AND INDUCES PROLIFERATION OF PROSTATE STROMAL CELLS

INTRODUCTION AND OBJECTIVES:Leptin is a metabolic peptide hormone produced by adipocytes, with assumed roles in proflieration of prostate cancer cells and of prostate cells in animal models of beni...

Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis

Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.

Protein Phosphatase 2A Reduces Cigarette Smoke-induced Cathepsin S and Loss of Lung Function.

Rationale: CTSS (cathepsin S) is a cysteine protease that is observed at higher concentrations in BAL fluid and plasma of subjects with chronic obstructive pulmonary disease (COPD). Objectives: To investigate whether CTSS is involved in the pathogenesis of cigarette smoke-induced COPD and determine whether targeting upstream signaling could prevent the disease. Methods: CTSS expression was investigated in animal and human tissue and cell models of COPD. Ctss-/- mice were exposed to long-term cigarette smoke and forced oscillation and expiratory measurements were recorded. Animals were administered chemical modulators of PP2A (protein phosphatase 2A) activity. Measurements and Main Results: Here we observed enhanced CTSS expression and activity in mouse lungs after exposure to cigarette smoke. Ctss-/- mice were resistant to cigarette smoke-induced inflammation, airway hyperresponsiveness, airspace enlargements, and loss of lung function. CTSS expression was negatively regulated by PP2A in human bronchial epithelial cells isolated from healthy nonsmokers and COPD donors and in monocyte-derived macrophages. Modulating PP2A expression or activity, with silencer siRNA or a chemical inhibitor or activator, during acute smoke exposure in mice altered inflammatory responses and CTSS expression and activity in the lung. Enhancement of PP2A activity prevented chronic smoke-induced COPD in mice. Conclusions: Our study indicates that the decrease in PP2A activity that occurs in COPD contributes to elevated CTSS expression in the lungs and results in impaired lung function. Enhancing PP2A activity represents a feasible therapeutic approach to reduce CTSS activity and counter smoke-induced lung disease.

Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness.

While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surrounding vasculature and subsequently extravasation, accelerating metastasis. Here, we show that nanoparticles induce endothelial leakiness through disruption of the VE-cadherin-VE-cadherin homophilic interactions at the adherens junction. We show that intravenously injected titanium dioxide, silica and gold nanoparticles significantly accelerate both intravasation and extravasation of breast cancer cells in animal models, increasing the extent of existing metastasis and promoting the appearance of new metastatic sites. Our results add to the understanding of the behaviour of nanoparticles in complex biological systems. The potential for NanoEL needs to be taken into consideration when designing future nanomedicines, especially nanomedicine to treat cancer.

Mojave Yucca (Yucca Schidigera Roezl) Effects on Female Reproduction a Review

Abstract Yucca is an important source of biologically active substances such as steroidal saponins and stilbenes providing many beneficial effects when administered to humans and other animals. These substances offer a great potential in the prevention and treatment of current civilized diseases as well as to their: antioxidant, hypocholesterolaemic, anti-inflammatory, phytoestrogenic, pro-apoptotic, anti-proliferative, and anti-carcinogenic properties. This review focuses on the roles of two main yucca constituent groups and their ability to modulate ovarian functions and female reproductive performance. Both the biological activity of yucca substances and the mechanisms of their actions on ovaries are still incompletely understood. Thus, the direct effects of yucca extract on ovarian cells in animal models under in vitro conditions, as well as actions after yucca consumption will be discussed.

Study of in vitro and in vivo free radical scavenging activity for radioprotection of cerium oxide nanoparticles

Nanoceria have shown numerous unique characteristics, such as biocompatibility and are excellent agents for biological applications. The aim of this study is to investigate cerium oxide nanoparticles for 2, 2- diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity and their ability to offer protection against ionizing radiation. In vitro antioxidant activity study of nanoceria particles has shown good free radical scavenging activity for DPPH radical assayed within a concentration range of 0.01 to 0.05 g/l, at higher concentrations of nanoparticles showed reverse trend in absorbance and inhibition indicating this finite rang of concentration is suitable for scavenging free radicals, also nanoparticles were found to have significant antioxidant capacity and thus can be used as potential radical scavenger against deleterious damages caused by the free radicals. The results of histopathological examination showed effectiveness of CeO2 nanoparticles in radioprotection of skin cells in animal models during radiation exposure.

Tissue Engineering in Achilles Tendon Reconstruction: A Systematic Review of Preclincal Studies.

Tissue engineering is now being used in Achilles tendon (AT) repair in animal models. There are many preclinical studies that have used different types of stem cells for AT repair. However, there are no systematic reviews that evaluate all these studies to see which type of stem cell provides the most improvement for AT repair in animal models. Sahni V et al.,(1) divided the multiple stem cell types into three broad categories; Tendon derived stem cells (TDSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). These three categories have been used in this systematic review to group the different stem cell types together and to also see which category of stem cells provide superior enhancement of AT repair. All studies that have focused on using different types of stem cells in animal models for AT repair and have also included an outcome measure to identify any improvement made with stem cells have been included in this systematic review. Online published articles from 1946 to January 2016 were searched using Ovid MEDLINE (R) and PubMed databases. Of the 181 articles found and assessed for eligibility, 15 articles met predefined selection criteria and were included in this systematic review. Stem cells can either augment current methods of surgical repair or can provide an alternative route for tendon regeneration because of their unique ability of improving histological characteristics and biomechanical properties. This systematic review shows that stem cells can provide an improvement in AT repair in animal models. Histological analysis of the tendon tissue as well as biomechanical tests such as ultimate failure load have been used to show this improvement in AT repair. Nevertheless, we do not know which type of stem cell, from the three broad categories, provides a superior enhancement of AT regeneration in animal models. Our results underscore a need for a head-to-head comparison of the different types of stem cells used in AT repair with or without current methods of surgical repair.

Retracted: Curcumin derivative L6H4 inhibits proliferation and invasion of gastric cancer cell line BGC‐823

Curcumin and its chalcone derivatives have well-known, explicit biological antitumor properties, such as instance antiproliferative and apoptotic effects via multiple molecular targets. In this study, we investigated the anticancer activity of curcumin derivative L6H4 (curcumin L6H4) on gastric cancer cells. Inhibitory effects of curcumin L6H4 on gastric cancer cells (BGC-823) were studied by the diphenyltetrazolium (MTT) assay, and cell apoptosis was detected by Annexin-V/propidium iodide (PI) staining and then analyzed by flow cytometry. A mouse xenotransplant gastric tumor model was established to detect the role of curcumin L6H4 in vivo. The apoptosis-related proteins p53, p21, Bax, and Bcl-2 in BGC-823 cells and mouse xenotransplant models treated with curcumin L6H4 were determined by Western blot analysis. Curcumin L6H4 can significantly inhibit the proliferation and induce the apoptosis of BGC-823 cells, thus enhancing the expression levels of p53, p21, Bax, and Bcl-2 noticeably in vivo and in vitro. Meanwhile, curcumin L6H4 can remarkably suppress the growth of tumor cells in animal models. These results suggest that curcumin derivative L6H4 has potent of antitumor properties in vitro or in vivo.

Realidade virtual no ensino de vias metabólicas

A literacia visual é a capacidade de compreender (ler) e usar (escrever) imagens e de pensar e aprender usando imagens (estáticas ou em movimento). A literacia visual e a visualização são componentes de aprendizagem chave na Bioquímica, porque essa ciência usa modelos de moléculas para explicar como as células funcionam. Muitos estudos têm mostrado que as tecnologias de visualização (TV) podem ser úteis para desenvolver a literacia visual. O termo "realidade virtual" pode ser definido como um ambiente tridimensional imersivo, interativo, multissensorial, centrado no espectador e gerado por computador que leva em conta a combinação de tecnologias necessárias para construir esses ambientes. Nós projetamos um aplicativo de Realidade Virtual (RV) chamado VRMET para ajudar no desenvolvimento de habilidades de literacia visual para entender e representar conceitos bioquímicos. O aplicativo VRMET foi desenvolvido usando o Unity3D, o SDK de realidade aumentada da Vuforia e o SDK do Google VR para Unity. As moléculas 3D foram obtidas da Protein Data Bank e ChemSpider e optimizadas utilizando o Blender. O VRMET usa um modelo 3D a escala de uma célula animal. VRMET requer um dispositivo com câmera. O usuário pode obter a App da Google Play Store. O VRMET tem duas cenas diferentes: a cena de realidade aumentada (RA) e uma cena da realidade virtual (RV). A cena de RA permite visualizar, desde vários ângulos diferentes um modelo em escala de uma célula animal. A cena RV permite acompanhar cada uma das reações da glicólise e ciclo do Krebs dentro do modelo celular. O VRMET permite que os alunos visualizem a estrutura molecular de substratos e produtos, percebendo assim as mudanças em cada molécula ao longo da via metabólica. Também permite observar onde ocorre cada via metabólica.

James Francis Tait. 1 December 1925—2 February 2014

James F. Tait FRS, with his wife Sylvia A. S. Tait FRS, made an indelible contribution to life science and medicine with the isolation and characterization of aldosterone, the most potent mineralocorticoid hormone produced by the mammalian adrenal cortex.Trained as a physicist, Tait turned to endocrinology during his first academic appointment at the Medical School of the Middlesex Hospital in London, where he met Sylvia. Their collaboration resulted in this major achievement within five years of his appointment, and they were both elected to fellowships of the Royal Society in 1959, when James was just 34.Shortly afterwards the Taits moved to the Worcester Foundation for Experimental Biology in Massachusetts, where he virtually created the study of hormone dynamics, using sophisticated techniques involving isotopically labelled hormone infusions. Many of his most highly cited papers stem from this period.In 1970 the Taits returned to the Middlesex Hospital, when he was appointed to the Joel Chair of Physics as Applied to Medicine. Here they continued studies on aldosterone and other adrenal steroids, using animal cell models.He continued to be active after retiring in 1982, and published a history of aldosterone in 2009. As a hobby he made a magnificent photographic record of the churches and abbeys of Yorkshire.Although, initially, recognition of aldosterone's clinical significance was slow, today it is thought that 10% of the incidence of essential hypertension is attributable to excess aldosterone. Aldactone, the earliest aldosterone antagonist, as well as more recently developed blockers, have proved effective in congestive heart failure. Sixty years after its discovery, aldosterone remains a rich and dynamic research field.

Role of CD1d- and MR1-Restricted T Cells in Asthma.

Innate T lymphocytes are a group of relatively recently identified T cells that are not involved in either innate or adaptive immunity. Unlike conventional T cells, most innate T lymphocytes express invariant T cell receptor to recognize exogenous non-peptide antigens presented by a family of non-polymorphic MHC class I-related molecules, such as CD1d and MHC-related molecule-1 (MR1). Invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells quickly respond to the antigens bound to CD1d and MR1 molecules, respectively, and immediately exert effector functions by secreting various cytokines and granules. This review describes the detrimental and beneficial roles of iNKT cells in animal models of asthma and in human asthmatic patients and also addresses the mechanisms through which iNKT cells are activated by environmental or extracellular factors. We also discuss the potential for therapeutic interventions of asthma by specific antibodies against NKT cells. Furthermore, we summarize the recent reports on the role of MAIT cells in allergic diseases.

GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study.

ObjectiveGrowth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion.Design and methodsNineteen consecutive patients with chronic thoracic complete SCI (AIS-A) were studied. Patients with low GH secretion were randomized in a double-blind, placebo-controlled study to receive either subcutaneous placebo injections or GH combined with physical therapy, for 6 months. Baseline cranial MRI, AIS motor and sensory scale, quality of life (spinal cord impact measurement) and modified Ashworth spasticity scale, quantitative sensory testing and neurophysiological exploration were assessed at baseline, 1, 3 and 6 months following treatment.ResultsThirteen had GH deficiency. Seven received GH, five placebo and one dropped out. Both groups were similar according to clinical and demographical data at baseline, except for greater GH deficiency in the GH treatment group. At 6th month, patients treated with GH showed a significant improvement in SCIM-III score and in electrical perception threshold up to the 5th level below SCI, on both sides compared to baseline.ConclusionsGHD seems to be frequent in traumatic SCI and GH replacement is safe without side effects. GH combined with physical therapy can improve quality of life of SCI patients and, strikingly, the sensory perception below lesion level.

Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.

PO-111 Non-contact electric fields inhibit the growth of breast cancer cells in animal models and induce local immune reaction

Introduction Non-contact electric fields namely Electro-capacitive Cancer Therapy (ECCT) exposure with low intensity and intermediate frequency (100 KHz) exerted between two capacitive electrodes increased the percentage of cell death of MCF-7 (39.45%). In addition, a pilot study of the safety and efficacy of ECCT performed in 9 C3H mice revealed significant tumour shrinkage of more than 67% in size. Histopathological analysis of the mammary glands showed macrophages and other immune cells infiltrate through the blood vessel in the area of breast tumour. We continued our study by using bigger sample size to observe the safety and efficacy of ECCT and local immune reaction after exposure. Material and methods All procedures involving animals were performed following approval by the Research Ethics Committee of Gadjah Mada University. Sprague Dawley rats were divided into three groups, each consisted of 9 rats. Two groups were DMBA-induced mammary tumours, and the other was placebo. One group of mammary tumour rats and the placebo ones were exposed to ECCT individually for 10 hours per day for 3 weeks. Tumour size was measured using a calliper. Blood sample were collected from rat orbital sinus for Complete Blood Count and blood chemistry tests. Finally, the rats were euthanized by using ketamine overdose for breast, kidney and liver histopathological analysis. Results and discussions After 3 weeks of exposure to ECCT, the growth rate of DMBA-induced mammary tumour was lower (0.01 cm 2 /day) than the non-therapy one (0.121 cm 2 /day) with statistical significance. The development of nodules of the therapy group was fluctuated indicating fluid intake in the nodules. After necropsy, the nodules were hollow which filled with fluid. Lymphocytes were seen in the area of breast cancer. Furthermore, cancer wounds have shrunk and dried up under exposure. No significant changes were observed in the complete blood count of the therapy groups. The activity of alanine transaminase and the level of bilirubin were not affected by the exposure, but not for creatinine level. However, no significant abnormality was found in the kidney structure, and the liver as well. Conclusion The results suggest that 100 kHz of non-contact electric fields at low intensity inhibit the growth of breast cancer in rat, and the ECCT was well tolerated by the animal. In addition, the exposure to ECCT also induces body immune system in the animal models to work against the tumour.

Postprandial increase in serum CA125 as a surrogate biomarker for early diagnosis of ovarian cancer

BackgroundCA125 is a prevalently used serum biomarker for detecting ovarian cancer over the last three decades. However, it has a significant deficiency in screening for early-stage cancer. With the purpose of exploring an effective approach to improve its performance in early diagnosis, we investigated the postprandial fluctuation pattern of cancer-derived CA125 and the underlying mechanism.MethodsIn two medical centers, 551 patients sonographically diagnosed with ovarian (adnexal) cysts (< 5 cm in diameter) were enrolled and divided into five disease groups (pelvic inflammatory cysts, retention cysts, endometrioma, benign/borderline cystadenoma and malignant cysts). The subtle differences in 1-h postprandial serum CA125 increases were compared between disease groups. A support vector machine (SVM)-based algorithm was used for refining the performance of CA125 postprandial increment. Ovarian cancer xenograft animal and cancer cell models were used to recapitulate the clinical findings and reveal the molecular basis of postprandial blood glucose and insulin in invoking the synthesis/secretion/re-absorption of CA125.ResultsPatients with ovarian cancer presented the highest postprandial increment 13.3 ± 0.7% (mean ± standard deviation) among the five disease groups. Using a CA125 increment ≥ 10% criterion, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) reached 83.3, 96.3, 61.1 and 98.8%, respectively, for early-stage ovarian cancer. This performance was further improved by the SVM-based CA125-increment algorithm, which exhibited 91.7% sensitivity, 99.2% specificity, 89.2% PPV and 99.4% NPV. Both modalities manifested diagnostic advantages over the traditional CA125 test (75.0% sensitivity, 25.4% specificity, 6.6% PPV and 93.6% NPV at the cut-off of 35 U/mL). Regarding the molecular basis, the postprandial blood glucose and insulin-invoked overexpression of Mucin 16 (encoding CA125) were demonstrated in animal and cancer cell models, which were mediated by the PI3K-Akt pathway. Nevertheless, a Mesothelin-based CA125 re-absorption behavior was noted in the treated cancer cells, which contributed to the over-drop following the postprandial peak of serum CA125.ConclusionsCancer-derived serum CA125 possesses a unique and distinctive postprandial pattern, that distinguishes it from the common CA125 elevation in a benign disease condition. The dynamic measurement/assessment strategy can achieve a discriminatory power superior to that of a static test.

PG201 protects mice from experimental autoimmune encephalomyelitis via suppression of effector T cell activation

BackgroundPG201 is a botanical formulation, approved as an ethical drug (ETC) phytomedicine for treatment of patients with osteoarthritis in Korea, following satisfactory phase II and phase III studies. This phytomedicine was previously been shown to possess significant anti-inflammatory activities, presumably via the control of Th1 and Th17 cells in animal models and in vitro cell culture systems. PurposeIn this study, the possibility of using PG201 to treat multiple sclerosis was explored. MethodsIn vitro, the effect of PG201 on the differentiation of CD4+ T cells was investigated. To test the effects of PG201 in vivo, a mouse experimental autoimmune encephalomyelitis (EAE) model was used. ResultsIt was found that PG201 treatment decreased the frequency of both CD4+T-bet+ and CD4+RORγt+T cells. In addition, the production of interferon- gamma (IFN-γ) and interleukin-17 (IL-17) from respective Th cells was highly reduced. The data from western blots showed that the amount of phosphorylated c-Jun, but not that of p65, was decreased by PG201. Consistently, the level of luciferase activity was downregulated by PG201 in activator protein 1 (AP-1) reporter plasmid assays. In mice pretreated with PG201, the day of onset was delayed and clinical symptoms of EAE were significantly improved in a dose-dependent manner. Consistent with these results, the number of infiltrated cells and the expression level of pro-inflammatory molecules were decreased. ConclusionThese findings indicate that PG201 may exert strong immunomodulatory effects in the EAE model via suppression of T cell activation, and that PG201 is a therapeutic reagent for the treatment of multiple sclerosis.

Mast Cells: Key Contributors to Cardiac Fibrosis.

Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis.

Inhibition of Notch1 induces population and suppressive activity of regulatory T cell in inflammatory arthritis.

Inhibition of Notch signalling has shown anti-inflammatory properties in vivo and in vitro models of rheumatoid arthritis (RA). The objective of this study was to determine whether Notch1 might play a role in regulating T-regulatory cells (Tregs) in animal models of RA.Methods: Collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) were induced in C57BL/6, Notch1 antisense transgenic (NAS) or DBA1/J mice. We examined whether pharmacological inhibitors of γ-secretase (an enzyme required for Notch1 activation) and antisense-mediated knockdown of Notch1 could attenuate the severity of inflammatory arthritis in CIA and CAIA mice. Proportions of CD4+CD25+Foxp3+ Treg cells were measured by flow cytometry. To assess the suppressive capacity of Treg toward responder cells, CFSE-based suppression assay of Treg was performed.Results: γ-secretase inhibitors and antisense-mediated knockdown of Notch1 reduced the severity of inflammatory arthritis in both CIA and CAIA mice. Pharmacological and genetic inhibition of Notch1 signalling induced significant elevation of Treg cell population in CIA and CAIA mice. We also demonstrated that inhibition of Notch signalling suppressed the progression of inflammatory arthritis through modulating the expansion and suppressive function of regulatory T (Treg) cells.Conclusion: Pharmacological and genetic inhibition of Notch1 signalling suppresses the progression of inflammatory arthritis through modulating the population and suppressive function of Treg cells in animal models of RA.