Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.

Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.
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软骨发生和成骨是一种连续的发育和谱系定义的生物学过程。

DOI:
10.1038/s41598-017-10048-z
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发表时间:
2017-08-30
期刊:
影响因子:
4.6
通讯作者:
Feng JQ
Feng JQ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jing Y;Jing J;Ye L;Liu X;Harris SE;Hinton RJ;Feng JQ

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虽然软骨形成和成骨被认为是出生后软骨内骨形成过程中两个独立的过程,但最近的研究表明,出生后骨生长中软骨细胞直接转化为骨细胞。在这里,我们使用细胞谱系追踪和多种体内方法来研究Bmpr 1a在软骨形成中的作用。我们的数据显示,当使用Aggrecan-Cre ERT 2在早期软骨细胞中一次性注射他莫昔芬删除Bmpr 1a时,骨骼形状,大小和结构发生了深刻的变化。我们观察到干骺端中软骨细胞衍生的骨细胞形成成骨细胞和骨细胞的谱系进展的缺乏。此外,我们证明了生长板软骨细胞和关节软骨细胞的关键贡献,不仅对长骨生长,而且对骨重建。相比之下,在具有3.6 Col 1-Cre的早期成骨细胞中删除Bmpr 1a对骨骼形状和大小几乎没有影响,除了成骨细胞和骨细胞的急剧增加,导致骨体积的显著增加。我们的结论是,软骨形成和成骨是一个连续的发展和谱系定义的生物学过程,其中Bmpr 1a信号在软骨细胞是必要的池或小生境的骨祖细胞,然后有助于在一个主要的方式整体骨形成和生长的形成。
Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre ERT2 in early cartilage cells with a one-time tamoxifen injection. We observed the absence of lineage progression of chondrocyte-derived bone cells to form osteoblasts and osteocytes in metaphyses. Furthermore, we demonstrated the key contribution of growth plate chondrocytes and articular chondrocytes, not only for long bone growth, but also for bone remodeling. In contrast, deleting Bmpr1a in early osteoblasts with 3.6 Col 1-Cre had little impact on skeletal shape and size except for a sharp increase in osteoblasts and osteocytes, leading to a profound increase in bone volume. We conclude that chondrogenesis and osteogenesis are one continuous developmental and lineage-defined biological process, in which Bmpr1a signaling in chondrocytes is necessary for the formation of a pool or niche of osteoprogenitors that then contributes in a major way to overall bone formation and growth.
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