Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes.
Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes.
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DOI：
10.1083/jcb.140.2.409
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发表时间：
1998-01-26
期刊：
影响因子：
--
通讯作者：
Kurisu K
中科院分区：
文献类型：
--
作者：
Enomoto-Iwamoto M;Iwamoto M;Mukudai Y;Kawakami Y;Nohno T;Higuchi Y;Takemoto S;Ohuchi H;Noji S;Kurisu K
为了研究骨形态发生蛋白（BMP）信号在软骨细胞内成骨过程中的作用，将BMP受体的显性负性（DN）形式分别引入从鸡胚胸骨下部和上部分离的未成熟和成熟软骨细胞中。我们发现对照组胸骨软骨细胞表达IA、IB和II型BMP受体以及BMP-4和-7。在未成熟的下胸骨（LS）软骨细胞中表达DN-II型BMP受体（称为DN-BMPR-II）导致分化功能丧失;与对照细胞相比，表达DN-BMPR-II的LS软骨细胞增殖更快，获得成纤维细胞形态，显示II型胶原和聚集蛋白聚糖基因表达很少，I型胶原基因表达上调。DN-BMPR-II在成熟的肥大上胸骨（US）软骨细胞中的表达引起了类似的效果。此外，DN-BMPR-II表达US细胞表现出很少的碱性磷酸酶活性和X型胶原基因表达，而对照US细胞产生碱性磷酸酶和X型胶原。表达DN-BMPR-II的US和LS软骨细胞对BMP-2治疗均无反应。当我们检测IA型和IB型BMP受体的DN形式的作用时，我们发现DN-BMPR-IA几乎没有作用，而DN-BMPR-IB具有与DN-BMPR-II相似但较弱的作用。我们的结论是，BMP信号，特别是II型BMP受体介导的信号，需要维持分化的表型，细胞增殖的控制，和肥大表型的表达。
To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II–expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II–expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II–expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.
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影响因子：
5.3
作者：
KOENIG, BB;COOK, JS;ROSENBAUM, JS
通讯作者：
ROSENBAUM, JS
影响因子：
2.6
作者：
Duprez, D;Bella, EJD;FrancisWest, PH
通讯作者：
FrancisWest, PH
影响因子：
2.9
作者：
FARNDALE, RW;SAYERS, CA;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
64.5
作者：
BENYA, PD;SHAFFER, JD
通讯作者：
SHAFFER, JD
影响因子：
10.5
作者：
Mishina, Y;Suzuki, A;Behringer, RR
通讯作者：
Behringer, RR