Vital Roles of β-catenin in Trans-differentiation of Chondrocytes to Bone Cells.
Vital Roles of β-catenin in Trans-differentiation of Chondrocytes to Bone Cells.
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β-连环蛋白在软骨细胞向骨细胞转分化中的重要作用
DOI：
10.7150/ijbs.23165
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发表时间：
2018
影响因子：
9.2
通讯作者：
Feng JQ
中科院分区：
文献类型：
--
作者：
Jing Y;Jing J;Wang K;Chan K;Harris SE;Hinton RJ;Feng JQ
最近的一项突破表明，软骨细胞向骨细胞的直接转分化通常发生在生长板、关节软骨和下颌髁突软骨中的软骨内骨形成过程中，这表明软骨发生和骨发生可能是一个连续的生物学过程，而不是两个独立的过程。然而，这种细胞转化的基因调控在很大程度上尚不清楚。在此，我们在R26 RTomato背景下采用软骨特异性β-连环蛋白功能丧失（β-连环蛋白fx/fx）和功能获得（β-连环蛋白fx（exon 3）/ fx（exon 3））模型（为了更好地追踪软骨细胞的细胞命运）来研究β-连环蛋白在细胞转分化中的作用。通过组织学、免疫组织化学和放射学方法结合细胞谱系追踪技术，我们发现Acan-CreERT 2或Col 10a 1-Cre缺失β-catenin导致下颌髁突生长过程中细胞转分化大大减少，软骨下骨体积显著减少。分子生物学研究表明，软骨细胞和骨细胞在细胞增殖和分化方面存在严重缺陷。功能获得研究（在出生后第7天、4周和6个月时，Acan-CreERT 2对β-连环蛋白的组成性激活）导致下颌髁中软骨细胞的更多骨细胞转分化，这是由于增殖增加和软骨细胞分化加速以及软骨基质内的初期成骨变化，导致形成不良的未成熟软骨下骨体积增加。这些结果支持了软骨和骨形成是一个连续过程的观点，其中β-catenin信号在髁突发育和生长过程中的软骨细胞向骨细胞的细胞转分化中起重要作用。
A recent breakthrough showing that direct trans-differentiation of chondrocytes into bone cells commonly occurs during endochondral bone formation in the growth plate, articular cartilage, and mandibular condylar cartilage suggests that chondrogenesis and osteogenesis are likely one continuous biological process instead of two separate processes. Yet, gene regulation of this cell transformation is largely unclear. Here, we employed cartilage-specific β-catenin loss-of-function (β-catenin fx/fx) and gain-of-function (β-catenin fx(exon3)/ fx(exon3)) models in the R26RTomato background (for better tracing the cell fate of chondrocytes) to study the role of β-catenin in cell trans-differentiation. Using histological, immunohistochemical, and radiological methods combined with cell lineage tracing techniques, we showed that deletion of β-catenin by either Acan-CreERT2 or Col10a1-Cre resulted in greatly reduced cell trans-differentiation with a significant decrease in subchondral bone volume during mandibular condylar growth. Molecular studies demonstrated severe defects in cell proliferation and differentiation in both chondrocytes and bone cells. The gain of function studies (constitutive activation of β-catenin with Acan-CreERT2 at ages of postnatal day 7, 4-weeks and 6-months) led to more bone cell trans-differentiation of chondrocytes in the mandibular condyle due to increased proliferation and accelerated chondrocyte differentiation with incipient osteogenic changes within the cartilage matrix, resulting in an increased volume of poorly-formed immature subchondral bone. These results support the notion that chondrogenesis and osteogenesis are one continuous process, in which β-catenin signaling plays an essential role in the cell trans-differentiation of chondrocytes into bone cells during mandibular condylar development and growth.
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DOI：
10.1038/labinvest.2015.142
发表时间：
2016-02
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Usami Y;Gunawardena AT;Iwamoto M;Enomoto-Iwamoto M
通讯作者：
Enomoto-Iwamoto M
影响因子：
1.2
作者：
Jing, Yan;Hinton, Robert J.;Feng, Jian Q.
通讯作者：
Feng, Jian Q.
在BAC-COL10A1启动子控制下，在肥厚软骨中CRE重组酶的特异性表达。
DOI：
10.1016/j.matbio.2008.07.001
发表时间：
2008-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Gebhard S;Hattori T;Bauer E;Schlund B;Bösl MR;de Crombrugghe B;von der Mark K
通讯作者：
von der Mark K
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。
影响因子：
4.6
作者：
Jing Y;Jing J;Ye L;Liu X;Harris SE;Hinton RJ;Feng JQ
通讯作者：
Feng JQ
DOI：
10.1002/jbmr.1639
发表时间：
2012-08
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Dao DY;Jonason JH;Zhang Y;Hsu W;Chen D;Hilton MJ;O'Keefe RJ
通讯作者：
O'Keefe RJ