The Peroxisome Proliferator–Activated Receptor γ Agonist Pioglitazone Preserves Bone Microarchitecture in Experimental Arthritis by Reducing the Interleukin‐17–Dependent Osteoclastogenic Pathway

Koufany, Meriem; Chappard, Daniel; Netter, Patrick; Bastien, Claire; Weryha, G.; Jouzeau, Jean‐Yves; Moulin, David

doi:10.1002/art.38130

Cited by 17 publications

(17 citation statements)

References 52 publications

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“…To understand the effect of PPARγ on alveolar bone remodelling during the periodontitis progression, we detected bone metabolism‐related factors by ELISA and immunohistochemistry and investigated the loss of alveolar bone by several methods. Using RGZ to activate PPARγ for 4 weeks, promoted the expression of ALP and BMP‐2, and reduced the RANKL/OPG ratio in serum, which were consistent with the findings in previous studies (Kim et al., ; Koufany et al., ). Nevertheless, after 8 weeks the results reversed with the decreased expression of ALP, BMP‐2 and the increased RANKL/OPG ratio with RGZ intervention.…”

Section: Discussionsupporting

confidence: 90%

“…Using RGZ to activate PPARγ for 4 weeks, promoted the expression of ALP and BMP-2, and reduced the RANKL/OPG ratio in serum, which were consistent with the findings in previous studies Koufany et al, 2013). Nevertheless, after 8 weeks the results reversed with the decreased expression of ALP, BMP-2 and the increased RANKL/OPG ratio with RGZ intervention.…”

Section: Discussionsupporting

confidence: 90%

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Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

Qiao

Wang

Huang

et al. 2018

J Clinic Periodontology

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

Qiao

Wang

Huang

et al. 2018

J Clinic Periodontology

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“…We already demonstrated a bone protective effect of pioglitazone in adjuvant-induced arthritis. 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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“…Regarding arthritis, at least to our knowledge, this is the first study to demonstrate the therapeutic effects of 15d-PGJ 2 in a mouse model of rheumatoid arthritis. In rats with adjuvant-induced arthritis (AIA), pioglitazone decreased bone destruction by controlling the circulating and local expression of IL-17, with a subsequent decrease in the RANKL/OPG ratio [21]. We hypothesized that the potential mechanism by which 15d-PGJ 2 decreased T cell proliferation could be mediated by inhibition of IL-2 secretion.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ^12,14-Prostaglandin J₂(15d-PGJ₂) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4⁺CD25⁻FOXP3⁺Cells

Carregaro

Napimoga

Peres

et al. 2016

Mediators of Inflammation

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The prostaglandin, 15-deoxy Δ12,14-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4+ Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25− population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25− cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.

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The Peroxisome Proliferator–Activated Receptor γ Agonist Pioglitazone Preserves Bone Microarchitecture in Experimental Arthritis by Reducing the Interleukin‐17–Dependent Osteoclastogenic Pathway

Cited by 17 publications

References 52 publications

Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

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

Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ^12,14-Prostaglandin J₂(15d-PGJ₂) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4⁺CD25⁻FOXP3⁺Cells

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The Peroxisome Proliferator–Activated Receptor γ Agonist Pioglitazone Preserves Bone Microarchitecture in Experimental Arthritis by Reducing the Interleukin‐17–Dependent Osteoclastogenic Pathway

Cited by 17 publications

References 52 publications

Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

Peroxisome proliferator‐activated receptor γ plays dual roles on experimental periodontitis in rats

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

Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ12,14-Prostaglandin J2(15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4+CD25−FOXP3+Cells

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Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ^12,14-Prostaglandin J₂(15d-PGJ₂) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4⁺CD25⁻FOXP3⁺Cells