Evidence for the presence of peroxisome proliferator-activated receptor (PPAR) α and γ and retinoid Z receptor in cartilage -: PPARγ activation modulates the effects of interleukin-1β on rat chondrocytes

Peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma, and retinoid acid receptor-related orphan receptor (ROR) alpha are members of the nuclear receptor superfamily of ligand-activated transcription factors. Although they play a key role in adipocyte differentiation, lipid metabolism, or glucose homeostasis regulation, recent studies suggested that they might be involved in the inflammation control and especially in the modulation of the cytokine production. This strongly suggests that these transcriptional factors could modulate the deleterious effects of interleukin-1 (IL-1) on cartilage. However, to date, their presence in cartilage has never been investigated. By quantitative reverse transcription-polymerase chain reaction, Western blot, and immunocytochemistry analysis, we demonstrated, for the first time, the presence of PPAR alpha, PPAR gamma, and ROR alpha in rat cartilage, at both mRNA and protein levels. Comparatively, the PPAR alpha mRNA content in cartilage was much lower than in the liver but not significantly different to that of the adipose tissue. PPAR gamma mRNA expression in cartilage was weak, when compared with adipose tissue, but similar to that found in the liver. ROR alpha mRNA levels were similar in the three tissues. mRNA expression of the three nuclear receptors was very differently modulated by IL-1 or mono-iodoacetate treatments. This indicates that they should be unequally involved in the effects of IL-1 on chondrocyte, which is in accordance with results obtained in other cell types. Indeed, we showed that 15d-PGJ2 mainly, but also the drug troglitazone, that are ligands of PPAR gamma could significantly counteract the decrease in proteoglycan synthesis and NO production induced by IL-1. By contrast, PPAR alpha ligands such as Wy-14,643 or clofibrate had no effect on this process. Therefore, the presence of PPAR gamma in chondrocytes opens up new perspectives to modulate the effects of cytokines on cartilage by the use of specific ligands. The function of the two other transcription factors, PPAR alpha and ROR alpha identified in chondrocytes remains to be explored.