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Bone morphogenetic proteins (BMP‐2 and BMP‐3) promote growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3T3‐E1 cells in vitro
Author(s) -
Hiraki Yuji,
Inoue Hiroyuki,
Shigeno Chohei,
Sanma Yuji,
Bentz Hanne,
Rosen David M.,
Asada Akira,
Suzuki Fujio
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650061215
Subject(s) - bone morphogenetic protein 2 , bone morphogenetic protein , alkaline phosphatase , endochondral ossification , microbiology and biotechnology , chemistry , chondrocyte , fibroblast growth factor , medicine , endocrinology , cartilage , biology , in vitro , receptor , anatomy , biochemistry , enzyme , gene
Abstract We studied the effects of highly purified bone morphogenetic protein 2 and 3 (BMP‐2 and −3) on growth plate chondrocytes and osteoblastic cells in vitro and compared to TGF‐β. A mixture of BMP‐2 and 3 (BMPs) strongly stimulated DNA synthesis of chondrocytes in the presence of fibroblast growth factor (FGF). BMPs induced rapid maturation of chondrocytes at a growing stage: BMPs transformed the cells into rounded cells and induced marked accumulation of cartilage matrix; TGF‐β slightly reduced matrix accumulation and changed cell morphology into spindle‐like in the presence of FGF. Moreover, exposure of chondrocytes to BMPs resulted in a dramatic increase of the putative ˜80 kD PTH receptors expressed on the cell surface. In multilayered chondrocytes at the calcifying stage, BMPs stimulated alkaline phosphatase (ALPase) activity but TGF‐β inhibited it. In osteoblastic MC3T3‐E1 cells, BMPs were found to be the most potent stimulator of ALPase activity thus far described: ALPase in the cells treated with ˜100 ng/ml of BMPs reached 5‐ to 20‐fold over the basal, whereas TGF‐β inhibited expression of ALPase activity in these cells. The stimulatory action of BMPs overrode the inhibition of ALPase activity by TGF‐β when the cells were incubated with TGF‐β and BMPs. BMPs also upregulated expression of the ˜80 kD PTH receptor on the cells. These results suggest that BMPs have unique biologic activities in vitro that lead to growth and phenotypic expression of cells playing a critical role in endochondral bone formation.