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Journal article
Functional Attributes of Synovial Fluid from Osteoarthritic Knee Exacerbate Cellular Inflammation and Metabolic Stress, and Fosters Monocyte to Macrophage Differentiation
Biomedicines, Vol.13(4), 878
2025
PMID: 40299511
Abstract
Background: Besides conventional norms that recognize synovial fluid (SF) as a joint lubricant, nutritional channel, and a diagnostic tool in knee osteoarthritis (kOA), based on the authors previous studies, this study aims to define functional role of SF in kOA. Methods: U937, a monocytic, human myeloid cell line, was induced with progressive grades of kOA SF, and the induction response was assessed on various pro-inflammatory parameters. This ‘SF challenge test model’ was further extended to determine the impact of SF on U937 differentiation using macrophage-specific markers and associated transcription factor genes. Mitochondrial membrane potential changes in SF-treated cells were evaluated with fluorescent JC-1 probe. Results: a significant increase in nitric oxide, matrix metalloproteinase (MMP) 1, 13, and vascular endothelial growth factor (VEGF)-1 was noted in the induced cells. A marked increase was seen in CD68, CD86, and the transcription factors –activator protein (AP)-1, interferon regulatory factor (IRF)-1, and signal transducer and activator of transcription (STAT)-6 in the SF-treated cells indicating active monocytes to macrophage differentiation. Reduced mitochondrial membrane potential was reflected by a reduced red-to-green ratio in JC-1 staining. Conclusions: these results underline the active role of OA SF in stimulating and maintaining inflammation in joint cells, fostering monocyte differentiation into pro-inflammatory macrophages. The decline in the membrane potential suggestive of additional inflammatory pathway in OA via the release of pro-apoptotic factors and damaged associated molecular patterns (DAMPs) within the cells. Overall, biochemical modulation of SF warrants a potential approach to intervene inflammatory cascade in OA and mitigate its progression.
Details
- Title
- Functional Attributes of Synovial Fluid from Osteoarthritic Knee Exacerbate Cellular Inflammation and Metabolic Stress, and Fosters Monocyte to Macrophage Differentiation
- Authors/Creators
- Vanshika Srivastava - Bharati Vidyapeeth Deemed UniversityAbhay Harsulkar - Bharati Vidyapeeth Deemed UniversityShama Aphale - Bharati Vidyapeeth Deemed UniversityAare Märtson - University of TartuSulev Kõks - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsPriya Kulkarni - University of FloridaShantanu Deshpande - Department of Orthopaedics, Bharati Hospital, Pune-Satara Road, Pune 411043, India
- Publication Details
- Biomedicines, Vol.13(4), 878
- Publisher
- MDPI
- Number of pages
- 18
- Identifiers
- 991005774733407891
- Copyright
- © 2025 by the authors.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.34 Orthopedics
- 1.34.255 Osteoarthritis
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Medicine, Research & Experimental
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology