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首页> 外文期刊>Osteoarthritis and cartilage >Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification.
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Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification.

机译：软骨细胞中β-catenin-LEF/ TCF信号通路的激活刺激异位软骨内骨化。

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Objective Members of the Wnt signaling protein family are expressed during cartilage development and skeletogenesis, but their roles and mechanisms of action in those processes remain unclear. Recently, we found that beta-catenin-LEF/TCF-dependent Wnt signaling stimulates chondrocyte maturation and hypertrophy and extracellular matrix calcification in vitro, events normally associated with cartilage-to-bone transition during skeletogenesis. Thus, we tested here whether activation of this pathway promotes endochondral ossification.Design Chick chondrocytes were infected with avian retroviral expression vectors encoding constitutive-active (CA) or dominant-negative (DN) forms of LEF, which activate or block beta-catenin-dependent Wnt signaling respectively. These cells and companion uninfected control cells were seeded into type I collagen gels and transplanted intramuscularly into nude mice. The resulting ectopic tissue masses forming over time in vivo were subjected to histological and molecular biological analyses.Results Transplantation of chick chondrocytes induced de novo endochondral bone formation. In situ hybridization and RT-PCR using species-specific probes and primers showed that the ectopic cartilaginous tissue was avian and thus donor-derived, whereas the bone tissue was mouse and thus host-derived. CA-LEF-expressing ectopic tissue masses contained abundant bone and marrow, while DN-LEF-expressing masses contained little bone and lacked marrow.Conclusions Activation of beta-catenin-LEF/TCF-dependent Wnt signaling accelerates chondrocyte maturation and replacement of cartilage by bone.
机译：目的Wnt信号蛋白家族的成员在软骨发育和骨骼生成过程中表达，但在这些过程中它们的作用和作用机制仍不清楚。最近，我们发现依赖β-catenin-LEF/ TCF的Wnt信号在体外刺激软骨细胞成熟，肥大和细胞外基质钙化，这些事件通常与骨骼形成过程中软骨向骨的转变有关。因此，我们在这里测试了该途径的激活是否促进软骨内骨化。设计小鸡软骨细胞感染了编码LEF的本构激活（CA）或显性阴性（DN）形式的禽逆转录病毒表达载体，该载体激活或阻断β-catenin-依赖的Wnt信令。将这些细胞和未感染的对照细胞接种到I型胶原凝胶中，然后肌内移植到裸鼠中。对随时间推移体内形成的异位组织肿块进行组织学和分子生物学分析。结果鸡软骨细胞的移植诱导了新生软骨内骨的形成。使用物种特异性探针和引物进行的原位杂交和RT-PCR表明，异位软骨组织是禽类，因此是供体来源的，而骨组织是小鼠，因此是宿主来源的。表达CA-LEF的异位组织块包含丰富的骨骼和骨髓，而表达DN-LEF的组织块包含很少的骨骼，缺乏骨髓。结论β-catenin-LEF/ TCF依赖性Wnt信号的激活可加速软骨细胞的成熟和软骨的置换骨。

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