GPRC5B通过调节自信号传递来保护骨关节炎
Liang He1, Ziwei Xu2, Xin Niu2
1Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai 201613, China.
Acta pharmaceutica Sinica. B
|July 31, 2023
概括
G蛋白结合受体类C组5组成员B (GPRC5B) 抑制软骨分解并促进再生,为骨关节炎 (OA) 治疗提供了一个新的治疗点.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 整形外科 整形外科 整形外科
背景情况:
- 骨关节炎 (OA) 是一种普遍的慢性疾病,影响全球数百万人.
- 目前的OA治疗主要是治疗疼痛和缓慢的软骨恶化,缺乏再生能力.
- 对于促进OA的软骨修复的治疗策略有着至关重要的需求.
研究的目的:
- 研究G蛋白结合受体类C组5成员B (GPRC5B) 在骨关节炎中的作用.
- 为了确定GPRC5B是否可以抑制软骨退化并促进软骨再生.
- 阐明GPRC5B在OA中的作用背后的分子机制.
主要方法:
- 在体外研究中,使用GPRC5B缺乏的红细胞来分析基因表达.
- 在体内研究中使用中介半月体 (DMM) 诱导的OA小鼠模型的不稳定.
- 在OA小鼠模型中使用lentiviral向量过度表达GPRC5B.
- 对AKT-mTOR-自信号通路的分析.
主要成果:
- 软骨细胞中的GPRC5B缺乏导致软骨 katabolic 基因的表达增加和 anabolic 基因的减少.
- 缺乏GPRC5B的小鼠表现出加剧的OA表型与改变的软骨基因表达.
- 通过抑制降解和促进再生,在DMM诱导的OA小鼠中过度表达GPRC5B减弱的软骨退化.
- 该研究确定了AKT-mTOR-自信号通路作为GPRC5B的下游.
结论:
- GPRC5B在关节炎的发病过程中起着至关重要的作用.
- 在GPRC5B中,它既具有保护性质,也具有重生性质的特性.
- 准GPRC5B激活是一种有前途的治疗策略,可以预防OA的进展.
相关概念视频
01:12GPCR Desensitization
6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
01:20The JAK-STAT Signaling Pathway
9.0K
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...
9.0K
02:58Regulated Protein Degradation
2.6K
2.6K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K