Abstract: ERR? is expressed in bone and cartilage in vivo and osteoblastic and chondrocytic cells in vitro. ERR? is a transcriptional activator of an osteoblast-associated osteopontin (OPN) and chondrocyte-associated (Sox9) gene in osteoblasts and chondrocytes respectively. Knockdown of ERR? expression by antisense oligonucleotide strategies in osteoblastic cell cultures reduces alkaline phosphatase activity. Together these findings indicate that ERR? is expressed in and plays a functional role in bone and cartilage. The results also indicate that agonists and antagonists of ERR? may be useful as therapeutic agents in a wide variety of diseases affecting bones and joints.