Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets

EBioMedicine

卷:72

Rajesh Botchu¹  Simon W Jones²  Amel Badoume³  Mark A Lindsay⁴  Patrick Hurley⁴  Dominika E Nanus⁴  Susanne N Wijesinghe⁴  Zubair Ahmed⁵  Andrea M Halsey⁵  Edward T Davis⁶ 

[1] Centre for Trauma Sciences Research, University of Birmingham, Birmingham B15 2TT, United Kingdom;

[2] The Royal Orthopaedic Hospital, Birmingham B31 2AP, United Kingdom;

[3] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom;

[4] Institute of Inflammation and Ageing, MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, United Kingdom;

[5] Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom;

关键词: scRNAseq;    Osteoarthritis;    Synovial fibroblasts;    Obesity;    Inflammation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets. Methods: Patients with early knee OA (n = 29) and end-stage knee OA (n = 22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. Fibroblast single cell RNA sequencing was performed using Chromium 10X and analysed using Seurat. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis and the effect of fibroblast secretome on neuronal growth assessed using rat DRGN. Findings: Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced greater survival and neurite outgrowth in dissociated adult rodent dorsal root ganglion neurons. Interpretation: Sites of patient-reported pain in knee OA exhibit a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients. Funding: This study was funded by Versus Arthritis, UK (21530; 21812)

【 授权许可】

Unknown