Retinoic acid induces matrix Gla protein gene expression in human cells

The objective of this study was to investigate the possible regulation of the vitamin K-dependent matrix Gla (gamma-carboxyglutamic acid) protein (MGP) by retinoic acid, a regulation suggested by the recent observation that the human MGP promoter has a perfect direct repeat which is nearly identical to the retinoic acid-responsive element in the retinoic acid receptor-beta gene. We report that retinoic acid strongly increases MGP mRNA levels in all human cells tested, including osteoblasts, articular cartilage chondrocytes, and fibroblasts. In osteoblastic cells, MGP mRNA levels are increased by 25-fold at 1 microM retinoic acid and achieve half-maximal levels at 0.1 microM hormone. MGP is a small secreted protein of unknown function that is synthesized in a wide variety of vertebrate tissues. The present results suggest that part of the known actions of retinoic acid on skin, bone, cartilage, and other tissues in the human may be mediated by the stimulation of MGP synthesis and the consequent effect of increased MGP secretion on nearby target cells.