Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling
文献类型：期刊论文
| 作者 | Yang, Yuanheng20,21; Hao, Cong21; Jiao, Tingying18,19; Yang, Zidan15,16,17; Li, Hui16,17,21; Zhang, Yuqing13,14; Zhang, Weiya11,12; Doherty, Michael11,12; Sun, Chuying10; Yang, Tuo9,16,17 |
| 刊名 | SCIENCE
 |
| 出版日期 | 2025-04-04 |
| 卷号 | 388期号:6742页码:13 |
| ISSN号 | 0036-8075 |
| DOI | 10.1126/science.adt0548 |
| 英文摘要 | Whether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)-the receptor of GUDCA-alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae, which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration-approved UDCA alleviated osteoarthritis through the gut FXR-joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota-GUDCA-intestinal FXR-GLP-1-joint pathway offers a potential strategy for osteoarthritis treatment. |
| WOS关键词 | ACID ; MICROBIOTA ; DIAGNOSIS ; HEALTH |
| 资助项目 | National Natural Science Foundation Regional Innovation and Development Joint Fund[U21A20352] ; National Natural Science Foundation of China[81930071] ; National Natural Science Foundation of China[82372474] ; National Natural Science Foundation of China[82222071] ; National Key Research and Development Project[2022YFC3601900] ; Natural Science Foundation of Hunan Province[2024JJ3047] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001500692500002 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318288]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wei, Jie; Xie, Cen; Zeng, Chao; Lei, Guanghua |
| 作者单位 | 1.Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China 2.Furong Lab, Bioinformat Ctr, Changsha, Peoples R China 3.Cent South Univ, Xiangya Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Changsha, Peoples R China 4.Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Lab Metab, Bethesda, MD USA 5.Cent South Univ, Xiangya Hosp, Dept Endocrinol, Endocrinol Res Ctr, Changsha, Peoples R China 6.Univ Toronto, Dept Mol Genet, Toronto, ON, Canada 7.Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada 8.Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China 9.Cent South Univ, Xiangya Hosp, Hlth Management Ctr, Changsha, Peoples R China 10.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Yuanheng,Hao, Cong,Jiao, Tingying,et al. Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling[J]. SCIENCE,2025,388(6742):13. |
| APA | Yang, Yuanheng.,Hao, Cong.,Jiao, Tingying.,Yang, Zidan.,Li, Hui.,...&Lei, Guanghua.(2025).Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling.SCIENCE,388(6742),13. |
| MLA | Yang, Yuanheng,et al."Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling".SCIENCE 388.6742(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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