Saffery, Nik Syazana Izyan and Genasan, Krishnamurithy and Chan, Chee Ken and Ayob, Khairul Anwar and Teo, Seow Hui and Al-Fayyadh, Mohamed Zubair Mohamed and Othman, Iekhsan and Abidin, Syafiq Asnawi Zainal and Murali, Malliga Raman and Raghavendran, Hanumantha Rao Balaji and Kamarul, Tunku (2022) Typical response of CD14(++)CD16(-) monocyte to knee synovial derived mediators as a key target to overcome the onset and progression of osteoarthritis. Frontiers in Medicine, 9. ISSN 2296-858X, DOI https://doi.org/10.3389/fmed.2022.904721.
Full text not available from this repository.Abstract
Synovitis with increased infiltration of immune cells is observed in osteoarthritis (OA). Given the inflammatory condition of synovitis, we explored the protein profile of OA synovium (OAS) and its effect on circulating monocytes activation, migration, and functional commitments. MethodsKnee-synovium was acquired from end-stage OA (N = 8) and trauma patients (Trauma baseline control: TBC; N = 8) for characterization using H&E histology, IHC (iNOS), LCMS-QTOF, and MALDI-imaging. Response of peripheral blood monocytes to OAS conditioned-media (OACM) was observed using transwell (n = 6). The migrated cells were captured in SEM, quantified using phase-contrast microphotographs, and their activation receptors (CCR2, CXCR2, CX3CR1, and CD11b), pro-inflammatory genes, and phagocytic potential were studied using flow cytometry, gene expression array/qPCR, and latex beads (LB) phagocytosis assay, respectively. ResultsThe Venn diagram displayed 119 typical proteins in OAS, while 55 proteins in TBCS. The STRING protein network analysis indicated distinctive links between proteins and gene ontology (GO) and revealed proteins associated with leukocyte-mediated immunity in OAS as compared to TBC. The MALDI-imaging showed typical localized proteins at 2234.97, 2522.61, 2627.21, 3329.50, and 3539.69 m/z and IHC confirmed pro-inflammatory iNOS expression in OA synovium. CD14(++)CD16(-) classical monocytes significantly migrated in OACM and expressed CCR2, CXCR2, and CD11b receptors, TNFRSF11A, MAPK1, S100A8, HSPB1, ITGAL, NFATC1, IL13RA1, CD93, IL-1 beta, TNF-alpha, and MYD88 genes and increased LB uptake as compared to SFM. ConclusionOur findings suggest that the differential protein profile of OA synovium and the classical monocytes migrated, activated, and functionally committed in response to these mediators could be of therapeutic advantage.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of higher education of Malaysia (MOHE) [FRGS/1/2020/SKK0/UM/03/2] |
| Uncontrolled Keywords: | Osteoarthritis; Synovium; Inflammation; MALDI-imaging; Proteomics; Monocytes |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 19 Sep 2023 06:37 |
| Last Modified: | 19 Sep 2023 06:37 |
| URI: | http://eprints.um.edu.my/id/eprint/41336 |
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