Estrogen receptor-related receptor-a (ERR-α) is dysregulated in inflammatory arthritis

Objectives. Subchondral bone loss is a characteristic feature of inflammatory arthritis. Recently, estrogen receptor-related receptor-α (ERR-α), an orphan nuclear receptor, has been found to be involved in activation of macrophages. We hypothesized that ERR-α which is expressed and also functional in articular chondrocytes, osteoblasts and osteoclasts, may be involved in rodent models of inflammatory arthritis. Methods. Erosive arthritis was induced in DBA/1 mice by injection of type II collagen in Freund's complete adjuvant. RNA was isolated from the bone and joints and expression of ERR-α and cartilage (GDF5 and Col2a1) and bone [bone sialoprotein (BSP) and osteocalcin (OCN)] markers was analysed by semi-quantitative PCR. Results. We report for the first time that the expression of ERR-α is dysregulated in bones and joints in a mouse model of inflammatory arthritis. Specifically, we show that ERR-α expression is down-regulated early in bone and later in joints of mice with type II CIA. Concomitantly, temporal changes were observed in GDF-5 and Col2a1 expression in joints following both initial injection and booster injection of type II collagen. Similarly, down-regulation of ERR-α mRNA expression in subchondral bone in mice with induced joint inflammation was also paralleled by down-regulation of markers of bone formation (BSP, OCN). Conclusions. These data suggest that dysregulation of ERR-α expression may precede and contribute to the destruction of cartilage and bone accompanying inflammatory arthritis.