Typical response of CD14 ++ CD16 - monocyte to knee synovial derived mediators as a key target to overcome the onset and progression of osteoarthritis.

Autor:	Saffery NSI; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Genasan K; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Chan CK; Mahkota Medical Centre, Jalan Merdeka, Melaka, Malaysia., Ayob KA; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Teo SH; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Al-Fayyadh MZM; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Othman I; Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Selangor, Malaysia., Abidin SAZ; Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Selangor, Malaysia., Raman MM; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Raghavendran HRB; Biomaterials Laboratory, Faculty of Clinical Research, Central Research Facility, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Kamarul T; Department of Orthopedic Surgery, National Orthopedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Advanced Medical and Dental Institute, University Sains Malaysia, Penang, Malaysia.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2022 Aug 29; Vol. 9, pp. 904721. Date of Electronic Publication: 2022 Aug 29 (Print Publication: 2022).
DOI:	10.3389/fmed.2022.904721
Abstrakt:	Objective: 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. Methods: Knee-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. Results: The 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-1β, TNF-α, and MYD88 genes and increased LB uptake as compared to SFM. Conclusion: Our 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Saffery, Genasan, Chan, Ayob, Teo, Al-Fayyadh, Othman, Abidin, Raman, Raghavendran and Kamarul.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu