与G蛋白结合的受体35刺激减少了人类骨细胞中骨质细胞的活性
Maria L Price1,2, Rachael A Wyatt1,2, Ana Crastin1,3
1Department of Metabolism and Systems Science and Centre for Diabetes, Endocrinology and Metabolism (CEDAM), University of Birmingham, Birmingham B15 2TT, United Kingdom.
JBMR plus
|September 22, 2025
概括
G蛋白结合受体35 (GPR35) 激动剂通过降低关键信号通路的调节来抑制人类骨质细胞活性和骨质再吸收. 这表明GPR35是新型骨质疏松症治疗的有希望的标.
科学领域:
- 骨生物学和骨质疏松症研究研究
- 细胞信号和受体药理学细胞信号和受体药理学
背景情况:
- G蛋白结合受体35 (GPR35) 在骨质疏松症中下调,在骨质量调节中起作用.
- GPR35在人类骨质细胞中表达,但其在这些细胞中的特定功能尚未完全理解.
研究的目的:
- 研究GPR35在人类骨质细胞功能中的作用,并确定其相关的信号通路.
- 评估GPR35激动剂作为骨质疏松症的潜在治疗药物.
主要方法:
- 人类外周血液单核细胞分化为骨质细胞.
- 评估了GPR35激动剂 (TCG1001,Zaprinast) 对骨质细胞活性,骨再吸收和基因表达的影响.
- 使用AlphaLISA测定和化学抑制剂/siRNA敲击,分析了信号通路激活.
- 骨质细胞抑制与目前的骨质疏松症药物进行了比较.
主要成果:
- GPR35激动剂显著降低了骨质细胞骨的再吸收和耐酸酸酶 (TRAP) 的活性.
- 当使用GPR35抗剂时,激素治疗降低了MMP9的表达,并防止了这些效应.
- 刺激GPR35降低了c-Src,Akt,CREB和NF-κB的酸化.
- 证明GPR35与Gi/o和G12/13信号通路结合在一起.
- GPR35激动剂抑制了TRAP活性,类似于德诺苏马布和阿伦德罗尼酸.
结论:
- GPR35在人类骨质细胞活性中起着重要的抑制作用.
- 已经阐明了参与GPR35抑制作用的信号通路.
- 通过减少骨质细胞活性,GPR35代表了骨质疏松症治疗的新且有前途的治疗标.
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