Expression of osteocalcin and its transcriptional regulators core-binding factor alpha 1 and MSX2 in osteoid-forming tumours

Osteosarcoma, fibrous dysplasia, and myositis ossificans contain osteoid-pr oducing cells that are not necessarily morphologically typical osteoblasts, Nevertheless these pathologic cells may share differentiation steps with o steoblasts at the molecular level. Osteocalcin, a bone-specific extracellul ar matrix protein, is a marker of mature osteoblasts. Osteocalcin is upregu lated by thr transcription factor core-binding factor alpha 1, which is res ponsible for commitment to the osteoblastic lineage, and is downregulated b y MSX2, a homeobox-containing transcription factor expressed during the ear ly proliferative phase of osteoblast differentiation. Semiquantitative reve rse transcription-polymerase chain reaction was used to compare expression levels of osteocalcin, core-binding factor alpha 1, and MSX2 in 34 osteosar coma, five fibrous dysplasia, and five myositis ossificans specimens, as we ll as in seven normal cortical bone samples. Despite normal or elevated lev els of core-binding factor alpha-1 expression in most specimens, osteocalci n expression was low or undetectable in most cases of osteosarcoma (25 of 3 4) and myositis ossificans (4 of 5). Single-strand conformation polymorphis m and sequencing did not identify any mutations in the DNA-binding domain o f core-binding factor alpha 1. However, a high level of MSX2 expression was demonstrated in these lesions, which may inhibit osteocalcin transcription . The presence of moderate levels of osteocalcin in fibrous dysplasia may c ontribute to the characteristic disconnected appearance of trabeculae in th at entity because osteocalcin is a negative regulator of bone formation.