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首页> 外文期刊>Biology Open >Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage
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Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage

机译：软骨内成骨细胞的双重途径：肥大软骨中鉴定的一种新的软骨细胞来源的骨祖细胞

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According to the general understanding, the chondrocyte lineage terminates with the elimination of late hypertrophic cells by apoptosis in the growth plate. However, recent cell tracking studies have shown that murine hypertrophic chondrocytes can survive beyond “terminal” differentiation and give rise to a progeny of osteoblasts participating in endochondral bone formation. The question how chondrocytes convert into osteoblasts, however, remained open. Following the cell fate of hypertrophic chondrocytes by genetic lineage tracing using BACCol10;Cre induced YFP -reporter gene expression we show that a progeny of Col10Cre-reporter labelled osteoprogenitor cells and osteoblasts appears in the primary spongiosa and participates – depending on the developmental stage – substantially in trabecular, endosteal, and cortical bone formation. YFP+ trabecular and endosteal cells isolated by FACS expressed Col1a1, osteocalcin and runx2, thus confirming their osteogenic phenotype. In searching for transitory cells between hypertrophic chondrocytes and trabecular osteoblasts we identified by confocal microscopy a novel, small YFP+Osx+ cell type with mitotic activity in the lower hypertrophic zone at the chondro-osseous junction. When isolated from growth plates by fractional enzymatic digestion, these cells termed CDOP (chondrocyte-derived osteoprogenitor) cells expressed bone typical genes and differentiated into osteoblasts in vitro . We propose the Col10Cre-labeled CDOP cells mark the initiation point of a second pathway giving rise to endochondral osteoblasts, alternative to perichondrium derived osteoprogenitor cells. These findings add to current concepts of chondrocyte-osteocyte lineages and give new insight into the complex cartilage-bone transition process in the growth plate.
机译：根据一般理解，软骨细胞谱系以生长板中的细胞凋亡消除晚期肥大细胞而终止。然而，最近的细胞追踪研究表明，鼠肥大性软骨细胞可以存活超过“终末”分化，并产生成骨细胞的后代参与软骨内骨形成。然而，如何将软骨细胞转化为成骨细胞的问题仍然存在。通过使用BACCol10的遗传谱系追踪追踪肥大性软骨细胞的细胞命运; Cre诱导的YFP -reporter基因表达，我们显示了Col10Cre-reporter标记的骨祖细胞和成骨细胞的后代出现在原发性海绵体内，并取决于发育阶段-参与在小梁，骨内膜和皮质骨形成中。通过FACS分离的YFP +小梁和骨内膜细胞表达Col1a1，骨钙蛋白和runx2，从而证实了它们的成骨表型。在寻找肥大性软骨细胞与小梁成骨细胞之间的瞬时细胞时，我们通过共聚焦显微镜鉴定了一种新的，小的YFP + Osx +细胞类型，在软骨骨连接处的肥大性下部区域具有有丝分裂活性。当通过分级酶消化从生长板中分离出来时，这些被称为CDOP（软骨细胞衍生的骨祖细胞）的细胞表达出骨骼典型基因，并在体外分化为成骨细胞。我们建议用Col10Cre标记的CDOP细胞标记第二条途径的起点，该途径产生软骨内成骨细胞，替代软骨膜来源的骨祖细胞。这些发现增加了软骨细胞-骨细胞谱系的当前概念，并为生长板中复杂的软骨-骨过渡过程提供了新的见解。

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