Rapid vitamin D-dependent PKC signaling shares features with estrogen-dependent PKC signaling in cartilage and bone.
Our work is based on the hypothesis that steroid hormones regulate cells through traditional cytoplasmic and nuclear receptor-mediated mechanisms, as well as by rapid effects that are mediated by membrane-associated pathways. We have used the rat costochondral growth plate chondrocyte culture model to study the signaling mechanisms used by steroid hormones to elicit rapid responses and to modulate gene expression in target cells. Our studies show that the secosteroids 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and 24,25-dihydroxyvitamin D3 [24R,25(OH)2D3], and the steroid hormone 17beta-estradiol, cause rapid increases in protein kinase C alpha (PKCalpha) activity, and many of the physiological responses of the cells to these regulators are PKC-dependent. Target cell specificity and the mechanisms by which PKCalpha is activated vary with each hormone. PKC activation initiates a signaling cascade that results in activation of the ERK1/2 family of mitogen activated protein kinases (MAPK), providing an alternate method for the steroids to modulate gene expression other than by traditional steroid hormone receptor-mediated pathways. In addition to their effects on growth plate chondrocytes, steroid hormones secreted by the cells also control events in the extracellular matrix through direct non-genomic regulation of matrix vesicles.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA. Barbara.Boyan@bme.gatech.edu
B D
BD
Boyan
Zvi
Z
Schwartz
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D011796:Quinacrine / Q000494:pharmacology; D015398:Signal Transduction; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D004967:Estrogens; D014807:Vitamin D; D004958:Estradiol; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D011796:Quinacrine