NONGENOMIC REGULATION OF EXTRACELLULAR-MATRIX EVENTS BY VITAMIN-D METABOLITES

Vitamin D metabolites appear to regulate chondrocytes and osteoblasts via a combination of genomic and nongenomic mechanisms. Specificity of the nongenomic response to either 1,25-(OH)(2)D-3 or 24,25-(OH)(2)D-3 may be conferred by the chemical composition of the target membrane and its fluid mosaic structure, by the presence of specific membrane receptors, or by the interaction with classic vitamin D receptors. Nongenomic effects have been shown to include changes in membrane fluidity, far,acid acylation and reacylation, arachidonic acid metabolism and prostaglandin production, calcium ion flux, and protein kinase C activity. Chondrocytes metabolize 25-(OH)D-3 to 1,25-(OH)(2)D-3 and 24,25-(OH)(2)D-3; production of these metabolites is regulated by both growth factors and hormones and is dependent on the state of cell maturation. 1,25-(OH)(2)D-3 and 24,25-(OH)(2)D-3 may interact directly with extracellular matrix Vesicles to regulate their function; in the matrix, including protease activity, resulting in matrix modification and calcification. Isolated matrix vesicles, produced by growth zone chondrocytes, can activate latent transforming growth factor-p when incubated with exogenous 1,25-(OH)(2)D-3. These observations suggest that nongenomic regulation of matrix vesicle structure and function may be a mechanism by which mesenchymal cells, like osteoblasts and chondrocytes, may modulate events in the extracellular matrix at sites distant from the cell surface. (C) 1994 Wiley-Liss, Inc.