Rheumatoid arthritis (RA), a systemic inflammatory and autoimmune disease of unknown etiology, is characterized by chronic inflammationof the synovium and erosions preferentially involving peripheral joints ( Palma et al.,2012).
Monocytes/macrophages infiltrate into the joints and produce various bioactive factors, including cytokines and MMPs, that cause persistent inflammation and lead to joint destruction (McInness et al.,2011).
Peroxisome proliferator activated receptor gamma (PPARg) belongs to the nuclear receptor super family of transcription factors. These transcription factors function as receptors for various lipid-soluble, small molecules that are most commonly generated as hormones or in the intermediary metabolic pathways (Szanto and Nagy.,2008).
Therefore, nuclear receptors function as metabolic sensors that in turn regulate gene expression programs according to the metabolic state of the cell or organ (Szanto and Nagy.,2008).
PPARγ was originally described in differentiating adipocytes (Tontonoz et al., 1994), later it was identified in other tissues (Kliewer et al., 1994) and a role in macrophages (Tontonoz et al., 1998) and dendritic cells (DCs) was also discovered (Szatmari et al., 2004; Szeles et al.,2007).
PPARγ was shown to be highly expressed in mouse thioglycolate-elicited macrophages and its natural and synthetic ligands inhibited the expression of several molecules involved in the inflammatory process like inducible nitric oxide synthase (iNOS), matrix metalloproteinase- 9 (MMP-9) and scavenger receptor A (Ricote et al., 1998). When similar effects were reported for the PPARg activators in human monocyte-derived macrophages the receptor attracted attention as a possible therapeutic target in inflammatory diseases (Jiang et al.,1998).
PPARγ is expressed by different cell types in the joints and plays a relevant anti-inflammatory role in various diseases ( Palma et al.,2012), Previous reports have also documented that PPARγ is expressed at both mRNA and protein levels by major cell populations in joints (Fahmi et al.,2001).