IGF1驱动Wnt诱导的关节损伤,是骨关节炎的潜在治疗标
Ana Escribano-Núñez1, Frederique M F Cornelis1, Astrid De Roover1
1Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Centre, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Nature communications
|October 25, 2024
概括
通过增加软骨细胞中的胰岛素类生长因子1 (IGF1),Wnt信号驱动关节炎. 阻断IGF1为骨关节炎提供了潜在的疾病修饰疗法,改善关节健康.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 类风湿病学 类风湿病学
背景情况:
- 骨关节炎 (OA) 是关节疼痛和残疾的主要原因.
- 目前的OA治疗只能治疗症状,缺乏疾病修饰疗法.
- 对于Wnt信号在OA病变发生过程中的作用尚不完全理解.
研究的目的:
- 调查Wnt信号对OA中联合破坏的作用机制.
- 为了确定Wnt诱导的OA的关键分子媒介.
- 探索OA的潜在治疗点.
主要方法:
- 研究了Wnt信号传递和胰岛素样生长因子1 (IGF1) 相互作用在关节性红细胞中.
- 使用了具有软骨特异性Igf1缺陷的小鼠模型.
- 分析了与IGF1基因促进体结合的Wnt转录因子TCF4.
- 研究了IGF1沉默在人类的OA胆固醇细胞.
主要成果:
- Wnt信号传递促进了IGF1在关节性肌体细胞中的转录.
- 在雄性小鼠中,IGF1是Wnt诱导的关节损伤的主要驱动因素.
- 从Wnt触发的OA和创伤后的OA受保护的雄性小鼠的软骨特异性Igf1删除.
- 在人体OA软骨细胞中,IGF1沉默恢复了健康的分子形状.
结论:
- 由Wnt诱导的IGF1是骨关节炎的关键调解者.
- 准Wnt诱导的IGF1是一个有前途的治疗策略,用于骨关节炎.
- 降低IGF1可能为骨关节炎治疗提供一种疾病修饰的方法.
相关概念视频
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
Canonical Wnt Signaling Pathway
8.7K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Genome-wide Association Studies-GWAS
12.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.6K


