Osteogenic differentiation is selectively promoted by morphogenetic signals from chondrocytes and synergized by a nutrient rich growth environment
Osteogenic differentiation is selectively promoted by morphogenetic signals from chondrocytes and synergized by a nutrient rich growth environment
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DOI：
10.1080/03008200390152142
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Einhorn, TA
中科院分区：
文献类型：
--
作者：
Gerstenfeld, LC;Barnes, GL;Einhorn, TA
在软骨内骨骼发育过程中，软骨的形成总是先于骨的形成。为了确定软骨细胞是否为成骨提供诱导信号，将 C3H10T1/2 间充质干细胞与软骨细胞、成骨细胞或成纤维细胞在膜分离的 Transwell 培养室中共培养。通过骨钙素 mRNA 的表达评估，骨生成在与软骨细胞共培养的 C3H10T1/2 细胞中被强烈诱导，但与成骨细胞或成纤维细胞共培养则不被诱导。有趣的是，虽然在与软骨细胞共培养的 C3H10T1/2 细胞中仅观察到成骨分化，但骨形态发生蛋白 (BMP)-7 处理诱导了骨骼细胞分化的有序软骨内进展，其中软骨形成分化先于成骨 2 至 4 天。营养丰富的生长环境可将共培养或 BMP-7 处理诱导的成骨分化增强 2 至 5 倍。营养增强的成骨分化与视网膜母细胞瘤介导的信号转导途径的激活有关。总之，这些结果表明，成骨是由软骨细胞产生的形态发生信号选择性诱导的，并且营养丰富的环境可增强 BMP-7 和共培养诱导的成骨分化。
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.