High dose of glucose promotes chondrogenesis via PKCalpha and MAPK signaling pathways in chick mesenchymal cells.
We investigated the molecular mechanism of the glucose effect on the regulation of chondrogenesis. Exposure of chick wing bud mesenchymal cells to high concentrations of glucose stimulated chondrogenesis 2-fold to 2.5-fold without affecting cell proliferation. Glucose increased protein levels and the membrane translocation of protein kinase C alpha (PKCalpha), leading to a reduction of extracellular signal-regulated kinase (ERK) phosphorylation. Phosphorylation of p38 was also increased in a PKC-independent manner by glucose treatment. Glucose also increased cell adhesion molecules such as fibronectin, integrin beta1, and N-cadherin at early stages and then decreased these adhesion molecules at later stages of chondrogenesis. These alterations in protein level of adhesion molecules and in the phosphorylation of mitogen-activated protein kinases by glucose were blocked by inhibition of PKC or p38 but were synergistically increased by the inhibition of ERK. Therefore, high doses of glucose induce the down-regulation of ERK activity via PKCalpha and the up-regulation of p38 and result in the stimulation of chondrogenesis of chick mesenchymal cells through modulating the expression of adhesion molecules.
Han
Yong-Su
YS
Department of Biology, College of Natural Sciences, Kyungpook National University, 702-701, Taegu, South Korea.
Bang
Ok-Sun
OS
Jin
Eun-Jung
EJ
Park
Jae-Han
JH
Sonn
Jong-Kyung
JK
Kang
Shin-Sung
SS
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D020219:Chondrogenesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D008648:Mesoderm / Q000187:drug effects* / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D015415:Biomarkers; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose