التفاصيل البيبلوغرافية
| العنوان: |
Machine Learning Reveals Synovial Fibroblast Genes Associated with Pain Affect Sensory Nerve Growth in Rheumatoid Arthritis. |
| المؤلفون: |
Bai Z, Bartelo N, Aslam M, Hale C, Blachere NE, Parveen S, Spolaore E, DiCarlo E, Gravallese E, Smith MH, Frank MO, Jiang CS, Zhang H, Lewis MJ, Sikandar S, Pitzalis C, Malfait AM, Miller RE, Zhang F, Goodman S, Darnell R, Wang F, Orange DE |
| مؤلفون مشاركون: |
Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network |
| المصدر: |
MedRxiv : the preprint server for health sciences [medRxiv] 2023 Aug 23. Date of Electronic Publication: 2023 Aug 23. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We identified a module of 815 genes associated with pain, using a novel machine learning approach, Graph-based Gene expression Module Identification (GbGMI), in samples from patients with longstanding RA, but limited synovial inflammation at arthroplasty, and validated this finding in an independent cohort of synovial biopsy samples from early, untreated RA patients. Single-cell RNA-seq analyses indicated these genes were most robustly expressed by lining layer fibroblasts and receptor-ligand interaction analysis predicted robust lining layer fibroblast crosstalk with pain sensitive CGRP+ dorsal root ganglion sensory neurons. Netrin-4, which is abundantly expressed by lining fibroblasts and associated with pain, significantly increased the branching of pain-sensitive CGRP+ neurons in vitro . We conclude GbGMI is a useful method for identifying a module of genes that associate with a clinical feature of interest. Using this approach, we find that Netrin-4 is produced by synovial fibroblasts in the absence of inflammation and can enhance the outgrowth of CGRP+ pain sensitive nerve fibers.
One Sentence Summary: Machine Learning reveals synovial fibroblast genes related to pain affect sensory nerve growth in Rheumatoid Arthritis addresses unmet clinical need. |
| تواريخ الأحداث: |
Date Created: 20230904 Latest Revision: 20230904 |
| رمز التحديث: |
20231215 |
| مُعرف محوري في PubMed: |
PMC10473790 |
| DOI: |
10.1101/2023.08.17.23294232 |
| PMID: |
37662384 |
| قاعدة البيانات: |
MEDLINE |
