Activation of protein kinase A is a pivotal step involved in both BMP-2- and cyclic AMP-induced chondrogenesis.
We studied the roles of protein kinase A (PKA) activation and cyclic AMP response element binding protein (CREB) phosphorylation in chondrogenesis using serum-free chicken limb bud micromass cultures as a model system. We showed the following points: 1) in micromass cultures, activation of PKA enhances chondrogenesis and increases the phosphorylation of CREB; 2) BMP-2, a chondrogenic stimulator, increases PKA activity and the level of phosphorylated CREB (P-CREB); 3) H8, a PKA inhibitor, inhibits chondrogenesis; 4) the chondrogenic activities of BMP-2 and cAMP are suppressed by H8; and 5) long-term TPA treatment (a protein kinase C (PKC) modulator) inhibits chondrogenesis and decreases the levels of CREB and P-CREB. These results suggest that activation of PKA is a physiological event during chondrogenesis that is involved in the chondrogenic effects of both BMP-2 and cyclic AMP (cAMP)-dependent pathways.
Lee
Y S
YS
Department of Pathology, University of Southern California, Los Angeles 90033, USA.
Chuong
C M
CM
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018878:Limb Buds / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases