昼夜调节器PER1通过激活炎症基因来抑制骨质细胞生成
Nobuko Katoku-Kikyo1,2, Elizabeth K Vu1,3, Samuel Mitchell1,3
1Stem Cell Institute, University of Minnesota.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
昼夜调节器PER1通过控制炎症来抑制骨损失. 准PER1可以在不破坏睡眠周期的情况下治疗骨疾病.
科学领域:
- 循环节生物学 日间生物
- 骨质免疫学 骨质免疫学
- 分子生物学分子生物学
背景情况:
- 扰乱昼夜节律与骨质疏松症等慢性疾病有关.
- 昼夜干扰对骨重塑的具体影响尚不清楚.
研究的目的:
- 研究核心昼夜调节器PER1在骨质细胞形成和骨重塑中的作用.
- 探索将昼夜节律扰乱与骨健康联系起来的分子机制.
主要方法:
- 在小鼠骨质细胞和相关细胞中Per1基因的条件淘汰.
- 在体外研究的骨质细胞形成与Per1枯竭.
- 对炎症基因表达的分析,包括炎症酶通路基因.
主要成果:
- 在小鼠中,骨质细胞的淘汰赛导致骨质量下降和骨质细胞/骨质细胞平衡的改变.
- 在实验室中,Per1枯竭通过降低17个炎症基因的调节促进了骨质细胞形成.
- 炎症途径基因的淘汰模仿了Per1的淘汰效应,揭示了一个机制.
结论:
- PER1 作为骨质细胞形成的抑制剂,可能通过调节炎症基因表达.
- PER1是与昼夜干扰相关的骨疾病的潜在治疗标,而不会引起一般的昼夜节律失常.
- 研究结果将昼夜调节与骨免疫学联系起来,并可能为炎症性骨疾病的治疗提供信息.
相关概念视频
Circadian Rhythms and Gene Regulation
4.5K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.5K
Osteoclasts in Bone Remodeling
3.9K
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...
3.9K
Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
NF-κB-dependent Signaling Pathway
9.8K
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...
9.8K
Hormones and Bone Tissue
3.7K
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...
3.7K
Prokaryotic Transcriptional Activators and Repressors
25.1K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
25.1K


