Sequential progression of the differentiation program by bone morphogenetic protein-2 in chondrogenic cell line ATDC5

Experimental Cell Research
C ShukunamiY Hiraki

Abstract

During embryonic development of long bones, chondroprogenitor cells exhibit the transitions of phenotype, i.e., from type I collagen-expressing cells to type II collagen-expressing chondrocytes through cellular condensation (early-phase differentiation) and then to type X collagen-expressing mineralizing chondrocytes (late-phase differentiation). The chondrogenic cell line ATDC5 displays the sequential transitions of phenotype in a synchronous manner in vitro. Taking advantage of the sequential differentiation, the effects of growth factors were evaluated at each differentiation step of ATDC5 cells. Among the factors examined, bone morphogenetic protein-2 (BMP-2) specifically stimulated a progression of the early-phase differentiation. Rounded chondrocytic cells were formed all over the culture plates by skipping out a cellular condensation stage. Fibroblast growth factor-2 stimulated growth of undifferentiated ATDC5 cells, but failed to stimulate overt chondrogenesis. The proliferation of differentiated cells ceased as cartilage nodules became maturated. At this stage, BMP-2 markedly up-regulated expression of type X collagen mRNA (a 9.1-fold increase) and alkaline phosphatase mRNA (a 7.5-fold increase) within 48 h. On the oth...Continue Reading

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