Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

Shahin, Dina; Toraby, Ehab El; Abdel-Malek, Hala; Boshra, Vivian; Elsamanoudy, Ayman Z.; Shaheen, Dalia

doi:10.4137/cmamd.s5951

Cited by 41 publications

(45 citation statements)

References 46 publications

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“…Accordingly, PPARɤ ligands have shown to have an anti-inflammatory activity in a variety of experimental and clinical studies of acute and chronic inflammation [32]. The present work comes in agreement with Dina et al (2011), who demonstrated that clinically, pioglitazone treatment showed significant improvement of CRP levels [33].…”

Section: Discussionsupporting

confidence: 95%

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis

Elgharabawy

Ahmed

Al-Najjar

2017

Biomedicine & Pharmacotherapy

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Section: Discussionsupporting

confidence: 95%

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis

Elgharabawy

Ahmed

Al-Najjar

2017

Biomedicine & Pharmacotherapy

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“…In response to loads at 0.2 and 0.5 N, elbow loading reduced the expression and activities of MMP-1 and MMP-13. On the contrary, it increased their mRNA and degenerative activity levels by higher loads at 2 N. We have previously shown that a natural joint rotation decreases enzyme activities of collagenases [12]. To our knowledge, this study demonstrated for the first time that moderate lateral loads to the synovial joint can suppress degenerative actions of MMPs in the articular cartilage.…”

Section: Discussionmentioning

confidence: 52%

“…Osteocalcin is an anabolic bone marker [11], which served to validate the efficacy of elbow loading in bone formation in the ulna. CITED2 is a transcription regulator that is reported to suppress the expression of MMP-1 and MMP-13 [12]. To evaluate various degenerative activities of MMPs, we determined total activities of collagenases and total activities of gelatinases, as well as MMP-1- and MMP-13-selective activities.…”

Section: Introductionmentioning

confidence: 99%

Moderate Joint Loading Reduces Degenerative Actions of Matrix Metalloproteinases in the Articular Cartilage of Mouse Ulnae

Sun

Zhao

Tanaka

et al. 2011

Connective Tissue Research

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Joint loading is a recently developed loading modality, which can enhance bone formation and accelerate healing of bone fracture. Since mechanical stimulation alters expression of matrix metalloproteinases (MMPs) in chondrocytes, a question addressed herein was, does joint loading alter actions of MMPs in the articular cartilage? We hypothesized that expression and activity of MMPs are regulated in a load–intensity-dependent manner and that moderate load scan downregulates MMPs. To test this hypothesis, a mouse elbow-loading model was employed. In the articular cartilage of an ulna, the mRNA levels of a group of MMPs as well as their degenerative activities were determined. The result revealed that elbow loading altered the expression and activities of MMPs depending on its loading intensity. Collectively, the data in this study indicate that 0.2 and 0.5 N joint loading significantly reduced the expression of multiple MMPs, that is, MMP-1, MMP-3, MMP-8, and MMP-13, and overall activities of collagenases or gelatinases in articular cartilage, while higher loads increased the expression and activity of MMP-1 and MMP-13. Furthermore, moderate loads at 1 N elevated the mRNA level of CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), but higher loads at 4 N did not induce a detectable amount of CITED2 mRNA. Since CITED2 is known to mediate the downregulation of MMP-1 and MMP-13, the result indicates that joint loading at moderate intensity reduces MMP activities through potential induction of CITED2. MMPs such as MMP-1 and MMP-13 are predominant collagenases in the pathology of osteoarthritis. Therefore, joint loading could offer an interventional regimen for maintenance of joint tissues.

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“…Indeed, pioglitazone decreased inflammatory-bone destruction and reduced bone micro-architecture in AIA rats by controlling circulating and local expression of IL-17 with a subsequent decrease of the (RANKL/OPG) ratio [13]. Of interest, three recent studies have demonstrated the efficacy of pioglitazone alone or in combination with methotrexate in RA patients [14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate vs pioglitazone: Comparative study of the anti-arthritic potencies of PPAR-alpha and PPAR-gamma agonists in rat adjuvant-induced arthritis

Koufany

Jouzeau

Moulin

2014

Bio-Medical Materials and Engineering

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BACKGROUND: Rheumatoid arthritis is characterized by synovial hyperplasia, inflammatory infiltration, cartilage destruction and juxta-articular as well as generalized bone demineralization. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily which behave as ligand-activated transcription factors in response to endogenous fatty acids and eicosanoids or isotype selective synthetic compounds as fibrates and thiazolidinediones. Beyond their key role in lipid metabolism, increased evidence has shown a role of the three isotypes in inflammatory modulation. We and others demonstrated previously that PPAR-gamma agonists reduced the severity of experimental polyarthritis and the overall inflammatory-induced bone loss. OBJECTIVE: To compare the anti-arthritic potencies of a PPAR-alpha agonist (fenofibrate, a lipid lowering drug) and a PPAR-gamma agonist (pioglitazone, formerly used as an antidiabetic drug) in rat adjuvant-induced arthritis. METHODS: Male Lewis rats were sensitized by an intra-dermal injection of 1 mg complete Freund's adjuvant at the basis of the tail and were treated orally for 21 days with fenofibrate 100 mg/kg/day (FENO) or pioglitazone 30 mg/kg/day (PIO), or with vehicle only. Arthritis severity was evaluated by clinical observations (oedema, clinical score, body weight). Global and femoral bone mineral density (BMD), femoral bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DEXA) before sensitization and at day 20. Synovial mRNA levels of IL-1beta and IL-6 were determined by real-time RT-PCR. RESULTS: Administration of fenofibrate (100mg/kg/d) and pioglitazone (30 mg/kg/d) significantly reduced hindpaw oedema and arthritis score. Treatment with fenofibrate exerted a better effect on clinical scoring. DEXA analysis revealed that pioglitazone and fenofibrate treatment to a greater extent, reduced inflammatory-bone loss and increased BMD versus vehicle-treated rats. Finally, we demonstrated that both agonists decreased synovial expression of IL-1beta and IL-6. CONCLUSION: Pioglitazone and fenofibrate decreased arthritis severity in adjuvant-induced arthritis. Both agonists partially protected animals from inflammatory induced-bone loss.

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Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

Cited by 41 publications

References 46 publications

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis

Moderate Joint Loading Reduces Degenerative Actions of Matrix Metalloproteinases in the Articular Cartilage of Mouse Ulnae

Fenofibrate vs pioglitazone: Comparative study of the anti-arthritic potencies of PPAR-alpha and PPAR-gamma agonists in rat adjuvant-induced arthritis

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