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)2D3 or 24,25-(OH)2D3 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, fatty acid acylation and reacylation, arachidonic acid metabolism and prostaglandin production, calcium ion flux, and protein kinase C activity. Chondrocytes metabolize 25-(OH)D3 to 1,25-(OH)2D3 and 24,25-(OH)2D3; production of these metabolites is regulated by both growth factors and hormones and is dependent on the state of cell maturation. 1,25-(OH)2D3 and 24,25-(OH)2D3 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-beta when incubated with exogenous 1,25-(OH)2D3. 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.
Boyan
B D
BD
Department of Orthopaedics, University of Texas Health Science Center at San Antonio 78284.
Dean
D D
DD
Sylvia
V L
VL
Schwartz
Z
Z
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology; D008954:Models, Biological; D010006:Osteoblasts / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011987:Receptors, Steroid / Q000502:physiology; D015290:Second Messenger Systems; D014807:Vitamin D / Q000502:physiology*
D011453:Prostaglandins; D011987:Receptors, Steroid; D014807:Vitamin D; D016718:Arachidonic Acid; D011493:Protein Kinase C; D002118:Calcium