Abstract: | 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, theexpression of mRNAs for proteins that are markers of osteoblastic differentiation, the deposition of calcium, and the formation ofmineralized nodules by ST2 cells. We investigated the mechanism wherebyascorbic acid induced the differentiation of ST2 cells. Inhibitors ofthe formation of collagen triple helices completely blocked the effectsof ascorbic acid on ST2 cells, an indication that matrix formation bytype I collagen is essential for the induction of osteoblasticdifferentiation of ST2 cells by ascorbic acid. We furthermore examinedthe effects of bone morphogenetic proteins (BMPs) on thedifferentiation of ST2 cells induced by ascorbic acid. Ascorbic acidhad no effect on the expression of mRNAs for BMP-4 and the BMPreceptors. However, a soluble form of BMP receptor IAinhibited the induction of ALPase activity by ascorbic acid. Theseresults suggest that ascorbic acid might promote the differentiation ofST2 cells into osteoblast-like cells by inducing the formation of amatrix of type I collagen, with subsequent activation of the signalingpathways that involve BMPs. |