Osteogenic differentiation is selectively promoted by morphogenetic signals from chondrocytes and synergized by a nutrient rich growth environment

被引:56
作者
Gerstenfeld, LC
Barnes, GL
Shea, CM
Einhorn, TA
机构
[1] Boston Univ, Med Ctr, Dept Orthopaed Surg, Orthopaed Res Lab, Boston, MA 02118 USA
[2] Harvard Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02115 USA
关键词
BMP; chondrocytes; endochondral bone; retinoblastoma;
D O I
10.1080/03008200390152142
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cartilage formation always precedes that of bone during endochondral skeletal development. To determine if chondrocytes provide inductive signals for osteogenesis, C3H10T1/2 mesenchymal stem cells were co-cultured in membrane separated transwell culture chambers with chondrocytes, osteoblasts, or fibroblasts. Osteogenesis, as assessed by the expression of osteocalcin mRNAs, was strongly induced in the C3H10T1/2 cells co-cultured with chondrocytes but not induced by co-culture with either osteoblasts or fibroblasts. Interestingly, while only osteogenic differentiation was observed in the C3H10T1/2 cells co-cultured with chondrocytes, bone morphogenetic protein (BMP)-7 treatment induced an ordered endochondral progression of skeletal cell differentiation in which chondrogenic differentiation preceded osteogenesis by 2 to 4 days. A nutrient enriched growth environment enhanced osteogenic differentiation induced by either co-culture or BMP-7 treatment 2- to 5-fold. Nutrient enhanced osteogenic differentiation was associated with an activation of the retinoblastoma-mediated signal transduction pathways. In summary, these results show that osteogenesis is selectively induced by morphogenetic signals produced by chondrocytes and that a nutrient rich environment enhances both BMP-7- and co-culture-induced osteogenic differentiation.
引用
收藏
页码:85 / 91
页数:7
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