Activation of PPARsα,β/δ, andγImpairs TGF-β1-Induced Collagens' Production and Modulat

Abstract

Background and Purpose. We investigated the potency of Peroxisome Proliferators-Activated Receptors (PPARs) α, β/δ, and γ agonists to modulate Transforming Growth Factor-β1 (TGF-β1-) induced collagen production or changes in Tissue Inhibitor of Matrix Metalloproteinase- (TIMP-) 1/Matrix Metalloproteinase (MMP) balance in rat chondrocytes embedded in alginate beads. Experimental Approach. Collagen production was evaluated by quantitative Sirius red staining, while TIMP-1 protein levels and global MMP (-1, -2, -3, -7, and -9) or specific MMP-13 activities were measured by ELISA and fluorigenic assays in culture media, respectively. Levels of mRNA for type II collagen, TIMP-1, and MMP-3 & 13 were quantified by real-time PCR. Key Results. TGF-β1 increased collagen deposition and type II collagen mRNA levels, while inducing TIMP-1 mRNA and protein expression. In contrast, it decreased global MMP or specific MMP-13 activities, while decreasing MMP-3 or MMP-13 mRNA levels. PPAR agonists reduced most of the effects of TGF-β1 on changes in collagen metabolism and TIMP-1/MMP balance in rat in a PPAR-dependent manner, excepted for Wy14643 on MMP activities. Conclusions and Implications. PPAR agonists reduce TGF-β1-modulated ECM turnover and inhibit chondrocyte activities crucial for collagen biosynthesis, and display a different inhibitory profile depending on selectivity for PPAR isotypes.

Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors

“…TZDs also inhibit NFassociated downstream COX-2 and iNOS signaling in osteoblasts, and thus might improve the inflammatory environment at ossification sites [254]. Recent findings show that extracellular matrix production by chondrocytes is controlled not only by PPAR but also by PPAR and PPAR / [255]. In an experimental model of rheumatoid arthritis, administration of the PPAR ligand fenofibrate reduces skeletal muscle wasting, thus alleviating the external symptoms of arthritis [256].…”

Membranes combining chitosan and natural-origin nanoliposomes for tissue engineering

“…Cell proliferation was assessed aer 7, 14 and 21 days of hMSCs culture onto the lms using the Hoechst assay, which allows cell DNA quantication. 55 Hoechst 33258 is a uorescent dye which binds to DNA allowing its quantication. Briey, hMSCs were harvested from 12-well plates coated with the lms.…”

“…Cell metabolic activity. Cell metabolic activity was measured using the MTT assay as described explained elsewhere, 55 where hMSCs seeded on standard plastic 96-well culture plates was used as reference value to normalize the results.…”

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice

“…PPAR γ is expressed in dermal fibroblasts and PPAR γ agonists, such as troglitazone, suppress the biosynthesis of matrix materials, such as collagen I or fibronectin, by inhibiting transforming growth factor (TGF)-β, a major factor in fibrosis [15]. Rosiglitazone (PPAR γ agonist) increases the expression of matrix metalloproteinase (MMP)-3 and MMP-13, while it decreases the expression of tissue inhibitor of metalloprotease (TIMP)-1 [16]. Furthermore, it was reported that 5,7-dimethoxyflavone, an activator of PPAR α/γ, not only inhibits the increase in MMP-1, MMP-2, MMP-9, and ROS induced by UV light in fibroblasts, but also suppresses inflammatory cytokines, such as interleukin (IL)-6 and IL-8 [17].…”