Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid.
The stromal cell line ST2, derived from mouse bone marrow, differentiated into osteoblast-like cells in response to ascorbic acid. Ascorbic acid induced alkaline phosphatase (ALPase) activity, the expression of mRNAs for proteins that are markers of osteoblastic differentiation, the deposition of calcium, and the formation of mineralized nodules by ST2 cells. We investigated the mechanism whereby ascorbic acid induced the differentiation of ST2 cells. Inhibitors of the formation of collagen triple helices completely blocked the effects of ascorbic acid on ST2 cells, an indication that matrix formation by type I collagen is essential for the induction of osteoblastic differentiation of ST2 cells by ascorbic acid. We furthermore examined the effects of bone morphogenetic proteins (BMPs) on the differentiation of ST2 cells induced by ascorbic acid. Ascorbic acid had no effect on the expression of mRNAs for BMP-4 and the BMP receptors. However, a soluble form of BMP receptor IA inhibited the induction of ALPase activity by ascorbic acid. These results suggest that ascorbic acid might promote the differentiation of ST2 cells into osteoblast-like cells by inducing the formation of a matrix of type I collagen, with subsequent activation of the signaling pathways that involve BMPs.
Research Center for Experimental Biology, Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
E
E
Otsuka
A
A
Yamaguchi
S
S
Hirose
H
H
Hagiwara
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D051379:Mice; D008903:Minerals / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
D019485:Bone Morphogenetic Proteins; D008903:Minerals; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D003094:Collagen; D052004:Bone Morphogenetic Protein Receptors; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid; D002118:Calcium