BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog
BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog
复制标题
DOI：
10.1016/s0736-0266(00)00017-6
复制
发表时间：
2001-01-01
影响因子：
2.8
通讯作者：
O'Keefe, RJ
中科院分区：
文献类型：
--
作者：
Grimsrud, CD;Romano, PR;O'Keefe, RJ
使用逆转录病毒载体将突变的BMP受体转染到培养的胚胎上胸骨软骨细胞中，以确定BMP信号传导是否是软骨细胞成熟和关键调节分子印度刺猬（Ihh）表达所需的。携带组成型活性成分CA、BMPR-IA和BMPR-IB的复制型禽逆转录病毒（RCAS）感染软骨细胞后，X型胶原和Ihh mRNA表达增强。加入PTHrP（一种已知的软骨细胞成熟抑制剂），在对照细胞中消除了X型胶原、BMP-6和1hmRh-A的表达。相反，用CA BMPR-IA或CA BMPR-IB感染的PTHrP处理的培养物具有低水平的BMP-6和X型胶原。但Ihh表达水平很高。虽然显性阴性（DN）BMPR-IA没有影响，DN BMPR-IB抑制X型胶原和BMP-6的表达，并降低碱性磷酸酶活性，即使在存在外源性添加的BMP-2和BMP-6。DN BMPR-IB也完全阻断Ihh表达。总体而言，DN BMPR-1B的作用模拟PTHrP的作用。为了确定BMP在软骨细胞成熟中是否有自分泌作用，用头蛋白和卵泡抑素（结合BMP-2/-4和BMP-6/-7的分子）处理培养物。分别而noggin和卵泡抑素则抑制重组BMP-2和BMP-6的作用。分别它们对培养物中软骨细胞的自发成熟仅有最小的影响，这表明BMP的一个以上亚群调节软骨细胞成熟。结果表明：ii）BMP信号传导刺激软骨细胞成熟：iii）BMP信号传导增加Ihh表达，与成熟效应无关;和（iii）BMP信号传导可以部分克服PTHrP对成熟的抑制作用。(C)2001骨科研究学会。由爱思唯尔科技有限公司出版。保留所有权利。
Mutant BMP receptors were transfected into cultured embryonic upper sternal chrondrocytes using retroviral vectors to determine if BMP signaling is required for chondrocyte maturation and the expression of a key regulatory molecule, indian hedgedog (Ihh). Chondrocytes infected with replication competent avian retroviruses (RCAS) viruses carrying constitutive active :CA BMPR-IA and BMPR-IB had enhanced expression of type X collagen and Ihh mRNA. Addition of PTHrP, a known inhibitor of chondrocyte maturation, abolished the expression of types X collagen, BMP-6, and Ihh mRh'As in control cells, In contrast, PTHrP treated cultures infected with of CA BMPR-IA or CA BMPR-IB had low levels of BMP-6 and type X collagen. but high levels of Ihh expression. Although dominant negative (DN) BMPR-IA had no effect, DN BMPR-IB inhibited the expression of type X collagen and BMP-6, and decreased alkaline phosphatase activity, even in the presence of exogenously added BMP-2 and BMP-6. DN BMPR-IB also completely blocked Ihh expression. Overall, the effect of DN BMPR-1B mimicked the effects of PTHrP. To determine if there is an autocrine role for the BMPs in chondrocyte maturation, the cultures were treated with noggin and follistatin, molecules that bind BMP-2/-4 and BMP-6/-7. respectively. While noggin and follistatin inhibited the effects of recombinant BMP-2 and BMP-6. respectively. they had only minimal effects on the spontaneous maturation of chondrocytes in culture, suggesting that more than one subgroup of BMPs regulates chondrocyte maturation. The results demonstrate that: ii) BMP signaling stimulates chondrocyte maturation: iii) BMP signaling increases Ihh expression independent of maturational effects; and (iii) BMP signaling can partially overcome the inhibitory effects of PTHrP on maturation. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.