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Effects of activin A and TGF-beta 1 on differentiation of osteoblast-like MC 3 T 3-E 1 cells



Effects of activin A and TGF-beta 1 on differentiation of osteoblast-like MC 3 T 3-E 1 cells



Shikwa Gakuho 101(6): 521-532



To elucidate the role activin A and transforming growth factor (TGF)-beta 1, which play important roles as coupling factors in bone remodeling, we investigated the effects of these cytokines on the differentiation of osteoblast-like MC 3 T 3-E 1 cells by analyzing the formation of bone nodules, alkaline phosphatase (ALP) activity and osteopontin (OPN) mRNA expression. Activin A increased the mineralized bone nodule accompanied by an acceleratedincrease in ALP activity, and it slightly stimulated OPN mRNA expression at the late stage of culture (21apprx28 days). TGF-beta 1 inhibited an increase in ALP activity and the formation of bone nodules in both untreated and activuin A treated cells. The inhibitory effect was predominant at the early stage of culture (7apprx14 days) with activin A. TGF-beta 1 increased OPN mRNA expression, which was synergistically cnhanced by the simultaneous treatment with activin A. When the cells were pretreated with TGF-beta 1, the synergistic effect by activin A on OPN mRNA expression was observed at the late stage of culture. While, when the cells were pretreated with activin A, the synergistic effect by TGF-beta 1 was observed at the early stage of culture. These results suggest that the cytokines regulate the differentiation of osteoblast-like cells depending on the stage of differentiation.

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