佩克托利纳基宁通过增强Wnt信号级联以PPARβ依赖的方式改善骨质疏松症
Jun Qian1, Qian Li2, Yangjie Song3
1Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Oral Implantology, Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
概括
皮托林里根因 (PEC) 通过激活氧酶增殖器激活受体β (PPARβ) 和增强Wnt信号传输,促进骨形成并减少骨损失. 这种天然化合物为骨质疏松症提供了潜在的新疗法.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 骨质疏松症是老年人常见的代谢性骨病.
- 过氧体增殖器激活受体β (PPARβ) 对于骨质细胞能量代谢至关重要,但其针对骨质疏松症的植物化合物的研究不足.
- 识别新的植物PPARβ激动剂对于开发新的骨质疏松症治疗方法至关重要.
研究的目的:
- 从植物来源发现一种强大的PPARβ激动剂.
- 为了研究已识别的化合物的抗骨质疏松作用.
- 阐明其治疗作用的潜在分子机制.
主要方法:
- 使用体外测试选植物化合物的PPARβ激动剂活性.
- 验证素原蛋白 (PEC) 对骨髓中酶体 stromal 细胞 (BMSCs) 的作用,通过西式涂抹和RNA-seq.
- 利用PPARβ和Wnt信号抑制剂来探索PEC的作用机制.
- 在体内给予PEC纳米颗粒 (PEC-NP) 来评估小鼠的抗骨质疏松作用.
主要成果:
- 标识了pectolinarigenin (PEC) 作为一种新型PPARβ激动剂,它促进了BMSCs的骨质分化.
- RNA-seq分析显示,PEC激活了Wnt和PPAR信号通路,以PPARβ依赖的方式增强了Wnt/β-catenin信号传递.
- 在体内研究表明,PEC-NP显著改善了骨质量,密度和骨质形成,同时在骨质疏松症模型中防止骨质损失,没有副作用.
结论:
- 通过增强依赖PPARβ的Wnt信号传递,PEC促进骨形成,并减少体外和体内骨损失.
- 这项研究为雌激素缺乏引起的骨质疏松症提供了新的治疗策略.
- 培托利纳基因因代表了一种有前途的天然化合物,用于预防和治疗骨质疏松症.
相关概念视频
01:17Hormones and Bone Tissue
2.7K
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
2.7K
01:40Bone Remodeling
38.3K
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
38.3K
02:54Canonical 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
01:31Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
01:41Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
01:31Osteoclasts in Bone Remodeling
2.9K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.9K